Quality assurance for Gamma Knife Perfexion using the Exradin W1 plastic scintillation detector and Lucy phantom.

The goal of this work is to validate the use of the Exradin W1 plastic scintillation detector (PSD) to measure profiles and output factors from Gamma Knife Perfexion collimators in a Lucy phantom. The Exradin W1 PSD has a small-volume, near-water-equivalent, energy-independent sensitive element. Output measurements were performed for all 3 collimators (4 mm, 8 mm, and 16 mm) of the Gamma Knife Perfexion system, and these measurements were compared to measurements made with an A16 ion chamber and an EBT3 film and to the nominal values. We showed that a configuration in which the focus or 'shot' moves while the detector remains fixed is essentially equivalent to a configuration in which the focus is fixed while the detector moves. A Lucy phantom containing a PSD was moved in small steps to acquire profiles in all three dimensions. EBT3 film was inserted in the Lucy phantom and exposed to a single shot for each collimator. The relative values for output factors measured with the PSD were 1.000, 0.892, and 0.795, for the 16 mm, 8 mm, and 4 mm collimators, respectively. The values measured with EBT3 film were 1.000, 0.881, and 0.793, and the values measured with the A16 ion chamber were 1.000, 0.883, and 0.727. The nominal output factors for the Gamma Knife Perfexion are 1.000, 0.900, and 0.814, respectively. There was excellent agreement between all profiles measured with the PSD and EBT3 as well as with the treatment planning system data provided by the vendor. In light of our results, the Exradin W1 PSD is well suited for beam quality assurance of a Gamma Knife Perfexion irradiator.

Phase 1 Study of Spinal Cord Constraint Relaxation With Single Session Spine Stereotactic Radiosurgery in the Primary Management of Patients With Inoperable, Previously Unirradiated Metastatic Epidural Spinal Cord Compression.

PURPOSE: We seek to establish the feasibility of using spine stereotactic radiosurgery (SSRS), allowing for spinal cord dose constraint relaxation, as the primary management of metastatic epidural spinal cord compression (MESCC) in inoperable patients. METHODS AND MATERIALS: Inoperable patients with thoracic MESCC and no history of radiation were enrolled on this prospective phase 1 single-institution protocol. SSRS was delivered to a histology-dependent prescription dose of 18 or 24 Gy. Incremental spinal cord constraint relaxation was performed from a Dmax cohort of 10 Gy up to 16 Gy only if tumor progression occurred and the risk of radiation-induced myelopathy (RM) remained lower than the risk of tumor progression. RESULTS: Thirty-two patients enrolled on the trial; 4, 12, 9, and 7 patients were in the 10 Gy, 12 Gy, 14 Gy, and 16 Gy cord Dmax cohorts, respectively. At baseline, there were 2 sites with MESCC grade 1A, 10 sites with grade 1B, 10 sites with grade 1C, 9 sites with grade 2, and 1 site with grade 3 disease. Among the 28 evaluable patients, the median overall survival was 28.6 months (95% confidence interval [CI], 9.2-48.0 months), and the 1-year local control was 89% (95% CI, 74%- 97%). With a median follow-up of 17 months, there were no cases of RM (upper 95% CI, 12%). In the cohort receiving a cord Dmax of 16 Gy, there were no cases of RM (upper 95% CI, 39%) with a median follow-up of 17 months (range, 12.7-21.0 months). CONCLUSIONS: SSRS is a safe and effective tool in patients with MESCC. In high-risk inoperable patients with MESCC receiving SSRS, dose constraint relaxation of the cord constraint dmax to 16 Gy may be considered to optimize local control, with the acknowledgment that this is based on 6 evaluable patients who received this dose in this trial.

Stereotactic radiosurgery for trigeminal pain secondary to recurrent malignant skull base tumors.

OBJECTIVE: The objective of this study was to assess outcomes after Gamma Knife radiosurgery (GKRS) re-irradiation for palliation of patients with trigeminal pain secondary to recurrent malignant skull base tumors. METHODS: From 2009 to 2016, 26 patients who had previously undergone radiation treatment to the head and neck received GKRS for palliation of trigeminal neuropathic pain secondary to recurrence of malignant skull base tumors. Twenty-two patients received single-fraction GKRS to a median dose of 17 Gy (range 15-20 Gy) prescribed to the 50% isodose line (range 43%-55%). Four patients received fractionated Gamma Knife Extend therapy to a median dose of 24 Gy in 3 fractions (range 21-27 Gy) prescribed to the 50% isodose line (range 45%-50%). Those with at least a 3-month follow-up were assessed for symptom palliation. Self-reported pain was evaluated by the numeric rating scale (NRS) and MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) pain score. Frequency of as-needed (PRN) analgesic use and opioid requirement were also assessed. Baseline opioid dose was reported as a fentanyl-equivalent dose (FED) and PRN for breakthrough pain use as oral morphine-equivalent dose (OMED). The chi-square and Student t-tests were used to determine differences before and after GKRS. RESULTS: Seven patients (29%) were excluded due to local disease progression. Two experienced progression at the first follow-up, and 5 had local recurrence from disease outside the GKRS volume. Nineteen patients were assessed for symptom palliation with a median follow-up duration of 10.4 months (range 3.0-34.4 months). At 3 months after GKRS, the NRS scores (n = 19) decreased from 4.65 ± 3.45 to 1.47 ± 2.11 (p < 0.001); MDASI-HN pain scores (n = 13) decreased from 5.02 ± 1.68 to 2.02 ± 1.54 (p < 0.01); scheduled FED (n = 19) decreased from 62.4 ± 102.1 to 27.9 ± 45.5 mcg/hr (p < 0.01); PRN OMED (n = 19) decreased from 43.9 ± 77.5 to 10.9 ± 20.8 mg/day (p = 0.02); and frequency of any PRN analgesic use (n = 19) decreased from 0.49 ± 0.55 to 1.33 ± 0.90 per day (p = 0.08). At 6 months after GKRS, 9 (56%) of 16 patients reported being pain free (NRS score 0), with 6 (67%) of the 9 being both pain free and not requiring analgesic medications. One patient treated early in our experience developed a temporary increase in trigeminal pain 3-4 days after GKRS requiring hospitalization. All subsequently treated patients were given a single dose of intravenous steroids immediately after GKRS followed by a 2-3-week oral steroid taper. No further cases of increased or new pain after treatment were observed after this intervention. CONCLUSIONS: GKRS for palliation of trigeminal pain secondary to recurrent malignant skull base tumors demonstrated a significant decrease in patient-reported pain and opioid requirement. Additional patients and a longer follow-up duration are needed to assess durability of symptom relief and local control.

Submillimeter alignment of more than three contiguous vertebrae in spinal SRS/SBRT with 6-degree couch.

The purpose of this study is to identify regions of spinal column in which more than three contiguous vertebrae can be reliably and quickly aligned within 1 mm using a 6-degree (6D) couch and full body immobilization device. We analyzed 45 cases treated over a 3-month period. Each case was aligned using ExacTrac x-ray positioning system with integrated 6D couch to be within 1° and 1 mm in all six dimensions. Cone-Beam computed tomography (CBCT) with at least 17.5 cm field of view (FOV) in the superior-inferior direction was taken immediately after ExacTrac positioning. It was used to examine the residual error of five to nine contiguous vertebrae visible in the FOV. The residual error of each vertebra was determined by expanding/contracting the vertebrae contour with a margin in millimeter integrals on the planning CT such that the new contours would enclose the corresponding vertebrae contour on CBCT. Submillimeter initial setup accuracy was consistently achieved in 98% (40/41) cases for a span of five or more vertebrae starting from T2 vertebra and extending caudally to S5. The curvature of spinal column along the cervical region and cervicothoracic junction was not easily reproducible between treatment and simulation. Fifty-seven percent (8/14) of cases in this region had residual setup error of more than 1 mm in nearby vertebrae after alignment using 6D couch with image guidance. In conclusion, 6D couch integrated with image guidance is convenient and accurately corrects small rotational shifts. Consequently, more than three contiguous vertebrae can be aligned within 1 mm with immobilization that reliably reproduces the curvature of the thoracic and lumbar spinal column. Ability of accurate setup is becoming less a concern in limiting the use of stereotactic radiosurgery or stereotactic body radiation therapy to treat multilevel spinal target.

Sparing of normal tissues with volumetric arc radiation therapy for glioblastoma: single institution clinical experience.

BACKGROUND: Patients with glioblastoma multiforme (GBM) require radiotherapy as part of definitive management. Our institution has adopted the use of volumetric arc therapy (VMAT) due to superior sparing of the adjacent organs at risk (OARs) compared to intensity modulated radiation therapy (IMRT). Here we report our clinical experience by analyzing target coverage and sparing of OARs for 90 clinical treatment plans. METHODS: VMAT and IMRT patient cohorts comprising 45 patients each were included in this study. For all patients, the planning target volume (PTV) received 50 Gy in 30 fractions, and the simultaneous integrated boost PTV received 60 Gy. The characteristics of the two patient cohorts were examined for similarity. The doses to target volumes and OARs, including brain, brainstem, hippocampi, optic nerves, eyes, and cochleae were then compared using statistical analysis. Target coverage and normal tissue sparing for six patients with both clinical IMRT and VMAT plans were analyzed. RESULTS: PTV coverage of at least 95% was achieved for all plans, and the median mean dose to the boost PTV differed by only 0.1 Gy between the IMRT and VMAT plans. Superior sparing of the brainstem was found with VMAT, with a median difference in mean dose being 9.4 Gy. The ipsilateral cochlear mean dose was lower by 19.7 Gy, and the contralateral cochlea was lower by 9.5 Gy. The total treatment time was reduced by 5 min. The difference in the ipsilateral hippocampal D100% was 12 Gy, though this is not statistically significant (P = 0.03). CONCLUSIONS: VMAT for GBM patients can provide similar target coverage, superior sparing of the brainstem and cochleae, and be delivered in a shorter period of time compared with IMRT. The shorter treatment time may improve clinical efficiency and the quality of the treatment experience. Based on institutional clinical experience, use of VMAT for the treatment of GBMs appears to offer no inferiority in comparison to IMRT and may offer distinct advantages, especially for patients who may require re-irradiation.

Internal validation of the prognostic index for spine metastasis (PRISM) for stratifying survival in patients treated with spinal stereotactic radiosurgery.

PURPOSE: We sought to validate the Prognostic Index for Spinal Metastases (PRISM), a scoring system that stratifies patients into subgroups by overall survival.Methods and materials: The PRISM was previously created from multivariate Cox regression with patients enrolled in prospective single institution trials of stereotactic spine radiosurgery (SSRS) for spinal metastasis. We assess model calibration and discrimination within a validation cohort of patients treated off-trial with SSRS for metastatic disease at the same institution. RESULTS: The training and validation cohorts consisted of 205 and 249 patients respectively. Similar survival trends were shown in the 4 PRISM. Survival was significantly different between PRISM subgroups (P<0.0001). C-index for the validation cohort was 0.68 after stratification into subgroups. CONCLUSIONS: We internally validated the PRISM with patients treated off-protocol, demonstrating that it can distinguish subgroups by survival, which will be useful for individualizing treatment of spinal metastases and stratifying patients for clinical trials.

Improved setup and positioning accuracy using a three-point customized cushion/mask/bite-block immobilization system for stereotactic reirradiation of head and neck cancer.

The purpose of this study was to investigate the setup and positioning uncertainty of a custom cushion/mask/bite-block (CMB) immobilization system and determine PTV margin for image-guided head and neck stereotactic ablative radiotherapy (HN-SABR). We analyzed 105 treatment sessions among 21 patients treated with HN-SABR for recurrent head and neck cancers using a custom CMB immobilization system. Initial patient setup was performed using the ExacTrac infrared (IR) tracking system and initial setup errors were based on comparison of ExacTrac IR tracking system to corrected online ExacTrac X-rays images registered to treatment plans. Residual setup errors were determined using repeat verification X-ray. The online ExacTrac corrections were compared to cone-beam CT (CBCT) before treatment to assess agreement. Intrafractional positioning errors were determined using prebeam X-rays. The systematic and random errors were analyzed. The initial translational setup errors were -0.8 ± 1.3 mm, -0.8 ± 1.6 mm, and 0.3 ± 1.9 mm in AP, CC, and LR directions, respectively, with a three-dimensional (3D) vector of 2.7 ± 1.4 mm. The initial rotational errors were up to 2.4° if 6D couch is not available. CBCT agreed with ExacTrac X-ray images to within 2 mm and 2.5°. The intrafractional uncertainties were 0.1 ± 0.6 mm, 0.1 ± 0.6 mm, and 0.2 ± 0.5 mm in AP, CC, and LR directions, respectively, and 0.0° ± 0.5°, 0.0° ± 0.6°, and -0.1° ± 0.4° in yaw, roll, and pitch direction, respectively. The translational vector was 0.9 ± 0.6 mm. The calculated PTV margins mPTV(90,95) were within 1.6 mm when using image guidance for online setup correction. The use of image guidance for online setup correction, in combination with our customized CMB device, highly restricted target motion during treatments and provided robust immobilization to ensure minimum dose of 95% to target volume with 2.0 mm PTV margin for HN-SABR.

Single-fraction versus multifraction spinal stereotactic radiosurgery for spinal metastases from renal cell carcinoma: secondary analysis of Phase I/II trials.

OBJECTIVE The objective of this study was to compare fractionation schemes and outcomes of patients with renal cell carcinoma (RCC) treated in institutional prospective spinal stereotactic radiosurgery (SSRS) trials who did not previously undergo radiation treatment at the site of the SSRS. METHODS Patients enrolled in 2 separate institutional prospective protocols and treated with SSRS between 2002 and 2011 were included. A secondary analysis was performed on patients with previously nonirradiated RCC spinal metastases treated with either single-fraction (SF) or multifraction (MF) SSRS. RESULTS SSRS was performed in 47 spinal sites on 43 patients. The median age of the patients was 62 years (range 38-75 years). The most common histological subtype was clear cell (n = 30). Fifteen sites underwent surgery prior to the SSRS, with laminectomy the most common procedure performed (n = 10). All SF SSRS was delivered to a dose of 24 Gy (n = 21) while MF regiments were either 27 Gy in 3 fractions (n = 20) or 30 Gy in 5 fractions (n = 6). The median overall survival duration for the entire cohort was 22.8 months. The median local control (LC) for the entire cohort was 80.6 months with 1-year and 2-year actuarial LC rates of 82% and 68%, respectively. Single-fraction SSRS correlated with improved 1- and 2-year actuarial LC relative to MF SSRS (95% vs 71% and 86% vs 55%, respectively; p = 0.009). On competing risk analysis, SF SSRS showed superior LC to MF SSRS (subhazard ratio [SHR] 6.57, p = 0.014). On multivariate analysis for LC with tumor volume (p = 0.272), number of treated levels (p = 0.819), gross tumor volume (GTV) coverage (p = 0.225), and GTV minimum point dose (p = 0.97) as covariates, MF SSRS remained inferior to SF SSRS (SHR 5.26, p = 0.033) CONCLUSIONS SSRS offers durable LC for spinal metastases from RCC. Single-fraction SSRS is associated with improved LC over MF SSRS for previously nonirradiated RCC spinal metastases.

Gamma Knife Stereotactic Radiosurgery for Brain Metastases Using Only 3 Pins.

BACKGROUND: Removal of a pin during Gamma Knife stereotactic radiosurgery (GK-SRS) may be necessary to prevent collision and allow treatment. OBJECTIVE: To investigate outcomes after GK-SRS for treatment of brain metastases using a head frame immobilized to the skull with only 3 pins. METHODS: Between 2009 and 2014, we retrospectively reviewed the records of 1971 patients and identified 20 patients with multiple brain metastases treated with GK-SRS in which 1 anterior pin was removed immediately before treatment of a single posterior lesion. GK-SRS was also delivered to 116 other lesions in these 20 patients using the standard 4 pins during the same session, serving as an internal control for comparison. Endpoints included local control, dosimetric parameters, toxicity, and overall survival. RESULTS: The median number of lesions treated per session was 6 (range, 2-14). The lesions treated using 3 pins were located in the occipital lobe (n = 14) or the cerebellum (n = 6). Median follow-up was 12.3 months. There was 1 local failure involving a control lesion. Lesions treated using 3 pins had a lower prescription isodose line. GK-SRS of a lesion using 3 pins did not cause any clinical toxicities or increase in radiographic edema or hemorrhage. CONCLUSION: Treating posteriorly located brain metastases with GK-SRS using only 3 pins provided excellent local control and no difference in treatment toxicity, which may make it a safe and reasonable option for lesions that may otherwise be difficult to treat.

Prospective validation of treatment accuracy using implanted fiducial markers for spinal stereotactic body radiation therapy.

In order to accurately assess positioning errors in spinal SBRT, many institutions employ bony-fusion based imaging techniques, such as the ExacTrac™ (Brain Lab) system, in conjunction with 3D verification (performed via CT-on-rails in our practice). We hypothesized that the use of implanted gold fiducial markers could improve the accuracy of patient positioning over bony fusion alone. We addressed this question prospectively, enrolling patients on an IRB-approved protocol. Gold seeds were implanted in the vertebral pedicles flanking the target level. At treatment, setup error was calculated using two methods-standard kV image fusion, and geometric fiducial-based projection, with independent CT-on-rails verification. Analyses of residual set-up error showed that fiducial-based setup agreed with fusion-based determination, but did not significantly reduce error. Offline 6D fusion of the treatment and planning CT illustrated residual rotational error using standard or fiducial based setup. We conclude that the ExacTrac and CT-on-rails platform yields highly accurate results for spinal SBRT setup, with reduced residual error than previously reported. While the addition of fiducials did not further reduce error, the bony fusion approach is now prospectively validated in comparison to implanted fiducials. Both bony fusion and fiducial marker methods are associated with residual rotational error, thus 3D verification remains an important component of spinal SBRT treatment.

Prospective evaluation of target and spinal cord motion and dosimetric changes with respiration in spinal stereotactic body radiation therapy utilizing 4-D CT.

PURPOSE: To assess the dosimetric effects of respiratory motion on the target and spinal cord in spinal stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Thirty patients with 33 lesions were enrolled on a prospective clinical protocol and simulated with both free-breathing and four-dimensional (4-D) computed tomography (CT). We studied the target motion using 4-D data (10 phases) by registering a secondary image dataset (phase 1 to 9) to a primary image dataset (phase 0) and analyzing the displacement in both translational and rotational directions. The study of dosimetric impacts from respiration includes both the effect of potential target and spinal cord motion and anatomic changes in the beam path. A clinical step-and-shoot IMRT plan generated on the free-breathing CT was copied to the 4-D datasets to evaluate the difference in the dose-volume histogram of target and normal tissues in each phase of a breathing cycle. RESULTS: Twenty three lesions had no motion in a breathing cycle; four lesions had anterior-posterior motion ≤ 0.2 mm; two lesions had lateral motion ≤ 0.2 mm; and eight lesions had superior-inferior motion, most ≤ 0.2 mm with the worst at 0.6 mm. The difference of maximum dose to 0.01 cm3 of spinal cord in different phases of a breathing cycle was within 20 cGy in worst case. Target volumes that received the prescription dose (V100) varied little, with deviations of V100 of each phase from the average CT < 1% in most cases. Only when lesions were close to the diaphragm (e.g., at T11) did the V100 deviate by about 7% in the worst case scenario. However, this was caused by a small dose difference of 20 cGy to part of the target volume. CONCLUSIONS: Breathing induced target and spinal cord motion is negligible compared with other setup uncertainties. Dose calculation using averaged or free-breathing CT is reliable when posterior beams are used.

Creation of a Prognostic Index for Spine Metastasis to Stratify Survival in Patients Treated With Spinal Stereotactic Radiosurgery: Secondary Analysis of Mature Prospective Trials.

PURPOSE: There exists uncertainty in the prognosis of patients following spinal metastasis treatment. We sought to create a scoring system that stratifies patients based on overall survival. METHODS AND MATERIALS: Patients enrolled in 2 prospective trials investigating stereotactic spine radiation surgery (SSRS) for spinal metastasis with ≥ 3-year follow-up were analyzed. A multivariate Cox regression model was used to create a survival model. Pretreatment variables included were race, sex, age, performance status, tumor histology, extent of vertebrae involvement, previous therapy at the SSRS site, disease burden, and timing of diagnosis and metastasis. Four survival groups were generated based on the model-derived survival score. RESULTS: Median follow-up in the 206 patients included in this analysis was 70 months (range: 37-133 months). Seven variables were selected: female sex (hazard ratio [HR] = 0.7, P=.02), Karnofsky performance score (HR = 0.8 per 10-point increase above 60, P = .007), previous surgery at the SSRS site (HR = 0.7, P=.02), previous radiation at the SSRS site (HR = 1.8, P=.001), the SSRS site as the only site of metastatic disease (HR = 0.5, P=.01), number of organ systems involved outside of bone (HR = 1.4 per involved system, P<.001), and >5 year interval from initial diagnosis to detection of spine metastasis (HR = 0.5, P < .001). The median survival among all patients was 25.5 months and was significantly different among survival groups (in group 1 [excellent prognosis], median survival was not reached; group 2 reached 32.4 months; group 3 reached 22.2 months; and group 4 [poor prognosis] reached 9.1 months; P < .001). Pretreatment symptom burden was significantly higher in the patient group with poor survival than in the group with excellent survival (all metrics, P < .05). CONCLUSIONS: We developed the prognostic index for spinal metastases (PRISM) model, a new model that identified patient subgroups with poor and excellent prognoses.

PRESAGE 3D dosimetry accurately measures Gamma Knife output factors.

Small-field output factor measurements are traditionally very difficult because of steep dose gradients, loss of lateral electronic equilibrium, and dose volume averaging in finitely sized detectors. Three-dimensional (3D) dosimetry is ideal for measuring small output factors and avoids many of these potential challenges of point and 2D detectors. PRESAGE 3D polymer dosimeters were used to measure the output factors for the 4 mm and 8 mm collimators of the Leksell Perfexion Gamma Knife radiosurgery treatment system. Discrepancies between the planned and measured distance between shot centers were also investigated. A Gamma Knife head frame was mounted onto an anthropomorphic head phantom. Special inserts were machined to hold 60 mm diameter, 70 mm tall cylindrical PRESAGE dosimeters. The phantom was irradiated with one 16 mm shot and either one 4 mm or one 8 mm shot, to a prescribed dose of either 3 Gy or 4 Gy to the 50% isodose line. The two shots were spaced between 30 mm and 60 mm apart and aligned along the central axis of the cylinder. The Presage dosimeters were measured using the DMOS-RPC optical CT scanning system. Five independent 4 mm output factor measurements fell within 2% of the manufacturer's Monte Carlo simulation-derived nominal value, as did two independent 8 mm output factor measurements. The measured distances between shot centers varied by ± 0.8 mm with respect to the planned shot displacements. On the basis of these results, we conclude that PRESAGE dosimetry is excellently suited to quantify the difficult-to-measure Gamma Knife output factors.

Effect of spine hardware on small spinal stereotactic radiosurgery dosimetry.

Monte Carlo (MC) modeling of a 6 MV photon beam was used to study the dose perturbation from a titanium rod 5 mm in diameter in various small fields range from 2 × 2 to 5 × 5 cm(2). The results showed that the rod increased the dose to water by ∼6% at the water-rod interface because of electron backscattering and decreased the dose by ∼7% in the shadow of the rod because of photon attenuation. The Pinnacle(3) treatment planning system calculations matched the MC results at the depths more than 1 cm past the rod when the correct titanium density of 4.5 g cm(-3) was used, but significantly underestimated the backscattering dose at the water-rod interface. A CT-density table with a top density of 1.82 g cm(-3) (cortical bone) is a practical way to reduce the dosimetric error from the artifacts by preventing high density assignment to them, but can underestimates the attenuation by the titanium rod by 6%. However, when multi-beam with intensity modulation is used in actual patient spinal stereotactic radiosurgery treatment, the dosimetric effect of assigning 4.5 instead of 1.82 g cm(-3) to titanium implants is complicated. It ranged from minimal effect to 2% dose difference affecting 15% target volume in the study. When hardware is in the beam path, density override to the titanium hardware is recommended.

Generalizable class solutions for treatment planning of spinal stereotactic body radiation therapy.

PURPOSE: Spinal stereotactic body radiation therapy (SBRT) continues to emerge as an effective therapeutic approach to spinal metastases; however, treatment planning and delivery remain resource intensive at many centers, which may hamper efficient implementation in clinical practice. We sought to develop a generalizable class solution approach for spinal SBRT treatment planning that would allow confidence that a given plan provides optimal target coverage, reduce integral dose, and maximize planning efficiency. METHODS AND MATERIALS: We examined 91 patients treated with spinal SBRT at our institution. Treatment plans were categorized by lesion location, clinical target volume (CTV) configuration, and dose fractionation scheme, and then analyzed to determine the technically achievable dose gradient. A radial cord expansion was subtracted from the CTV to yield a planning CTV (pCTV) construct for plan evaluation. We reviewed the treatment plans with respect to target coverage, dose gradient, integral dose, conformality, and maximum cord dose to select the best plans and develop a set of class solutions. RESULTS: The class solution technique generated plans that maintained target coverage and improved conformality (1.2-fold increase in the 95% van't Riet Conformation Number describing the conformality of a reference dose to the target) while reducing normal tissue integral dose (1.3-fold decrease in the volume receiving 4 Gy (V(4Gy)) and machine output (19% monitor unit (MU) reduction). In trials of planning efficiency, the class solution technique reduced treatment planning time by 30% to 60% and MUs required by ∼20%: an effect independent of prior planning experience. CONCLUSIONS: We have developed a set of class solutions for spinal SBRT that incorporate a pCTV metric for plan evaluation while yielding dosimetrically superior treatment plans with increased planning efficiency. Our technique thus allows for efficient, reproducible, and high-quality spinal SBRT treatment planning.

Stereotactic body radiation therapy for management of spinal metastases in patients without spinal cord compression: a phase 1-2 trial.

BACKGROUND: Spinal stereotactic body radiation therapy (SBRT) is increasingly used to manage spinal metastases, yet the technique's effectiveness in controlling the symptom burden of spinal metastases has not been well described. We investigated the clinical benefit of SBRT for managing spinal metastases and reducing cancer-related symptoms. METHODS: 149 patients with mechanically stable, non-cord-compressing spinal metastases (166 lesions) were given SBRT in a phase 1-2 study. Patients received a total dose of 27-30 Gy, typically in three fractions. Symptoms were measured before SBRT and at several time points up to 6 months after treatment, by the Brief Pain Inventory (BPI) and the M D Anderson Symptom Inventory (MDASI). The primary endpoint was frequency and duration of complete pain relief. The study is completed and is registered with ClinicalTrials.gov, number NCT00508443. FINDINGS: Median follow-up was 15·9 months (IQR 9·5-30·3). The number of patients reporting no pain from bone metastases, as measured by the BPI, increased from 39 of 149 (26%) before SBRT to 55 of 102 (54%) 6 months after SBRT (p<0·0001). BPI-reported pain reduction from baseline to 4 weeks after SBRT was clinically meaningful (mean 3·4 [SD 2·9] on the BPI pain-at-its-worst item at baseline, 2·1 [2·4] at 4 weeks; effect size 0·47, p=0·00076). These improvements were accompanied by significant reduction in opioid use during the first 6 months after SBRT (43 [28·9%] of 149 patients with strong opioid use at baseline vs 20 [20·0%] of 100 at 6 months; p=0·011). Ordinal regression modelling showed that patients reported significant pain reduction according to the MDASI during the first 6 months after SBRT (p=0·00003), and significant reductions in a composite score of the six MDASI symptom interference with daily life items (p=0·0066). Only a few instances of non-neurological grade 3 toxicities occurred: nausea (one event), vomiting (one), diarrhoea (one), fatigue (one), dysphagia (one), neck pain (one), and diaphoresis (one); pain associated with severe tongue oedema and trismus occurred twice; and non-cardiac chest pain was reported three times. No grade 4 toxicities occurred. Progression-free survival after SBRT was 80·5% (95% CI 72·9-86·1) at 1 year and 72·4% (63·1-79·7) at 2 years. INTERPRETATION: SBRT is an effective primary or salvage treatment for mechanically stable spinal metastasis. Significant reductions in patient-reported pain and other symptoms were evident 6 months after SBRT, along with satisfactory progression-free survival and no late spinal cord toxicities. FUNDING: National Cancer Institute of the US National Institutes of Health.

Salvage craniospinal irradiation with an intensity modulated radiotherapy technique for patients with disseminated neuraxis disease.

PURPOSE: To report the use and results of a novel intensity modulated radiotherapy (IMRT)-based technique used for salvage craniospinal irradiation (CSI) in 6 patients who developed neuraxis disease after initial high-dose conformal radiotherapy (RT) to the brain. METHODS AND MATERIALS: After Institutional Review Board approval, all patients treated for disseminated leptomeningeal disease with salvage CSI using IMRT with conventional external beam radiotherapy were identified. The medical records and radiotherapy dosimetry were reviewed. Tolerance, morbidity, tumor control, and overall survival were evaluated. RESULTS: Six patients who received IMRT-based salvage CSI were identified. The median age was 6.5 years (range 2- 34 years) at initial RT and 7.7 years (range, 3-35 years) at salvage CSI. Disease progression necessitating salvage CSI was noted at a median of 10 months (range, 1-26 months) from the initial RT. The original disease site remained well controlled in all 6 patients. The median dose of the initial RT treatment was 52 Gy (range, 30.6-60 Gy). Salvage CSI dose was 36 Gy in 20 fractions in all 6 patients. IMRT was used to treat the cranial contents excluding the previously treated area. Five pediatric patients received electron beams to spine and 1 adult patient received photon beams to spine. IMRT allowed a conformal and uniform dose distribution to the target tissue while excluding previously treated areas. Salvage CSI dose of 36 Gy, delivered using IMRT and 36 Gy using electrons or photons to the spine, proved effective in providing good control of the disease. CONCLUSIONS: This technique of salvage CSI was effective in this patient cohort for leptomeningeal dissemination occurring outside of an area of focal irradiation. The technique was well tolerated and thus far has not been associated with any significant toxicity. Salvage therapy has been effective in 4 of the 6 patients thus far.

Toward a better understanding of the gamma index: Investigation of parameters with a surface-based distance method.

PURPOSE: The purpose of this work was to clarify the interactions between the parameters used in the γ index with the surface-based distance method, which itself can be viewed as a generalized version of the γ index. The examined parameters included the distance to agreement (DTA)/dose difference (DD) criteria, the percentage used as a passing criterion, and the passing percentage for given DTA/DD criteria. The specific aims of our work were (1) to understand the relationships between the parameters used in the γ index, (2) to determine the detection limit, or the minimum detectable error, of the γ index with a given set of parameters, and (3) to establish a procedure to determine parameters that are consistent with the capacity of an IMRT QA system. METHODS: The surface-based distance technique with dose gradient factor was derived, and then the relationship between surface-based distance and γ index was established. The dose gradient factor for plans and measurements of 10 IMRT patients, 10 spine stereotactic radiosurgery (SRS) patients, and 3 Radiological Physics Center (RPC) head and neck phantom were calculated and evaluated. The detection limits of the surface-based distance and γ index methods were examined by introducing known shifts to the 10 IMRT plans. RESULTS: The means of the dose gradient factors were 0.434 mm/% and 0.956 mm/% for the SRS and IMRT plans, respectively. Key quantities (including the mean and 90th and 99th percentiles of the distance distribution) of the surface-based distance distribution between two dose distributions were linearly proportional to the actual shifts. However, the passing percentage of the γ index for a given set of DTA/DD criteria was not associated with the actual shift. For IMRT, using the standard quality assurance criteria of 3 mm/3% DTA/DD and a 90% passing rate, we found that the detection limit of the γ index in terms of global shift was 4.07 mm/4.07 % without noise. CONCLUSIONS: Surface-based distance is a direct measure of the difference between two dose distributions and can be used to evaluate or determine parameters for use in calculating the γ index. The dose gradient factor represents the weighting between spatial and dose shift and should be determined before DTA/DD criteria are set. The authors also present a procedure to determine γ index parameters from measurements.

A quality assurance procedure to evaluate cone-beam CT image center congruence with the radiation isocenter of a linear accelerator.

A quality assurance (QA) procedure was developed to evaluate the congruence between the cone-beam computed tomography (CBCT) image center and the radiation isocenter on a Varian Trilogy linac. In contrast to the published QA procedures, this method did not require a ball bearing (BB) phantom to be placed exactly at the radiation isocenter through precalibrated room lasers or light field crosshairs. The only requirement was that the BB phantom be in a stationary position near the radiation isocenter during the image acquisition process. The radiation isocenter was determined with respect to the center of the BB using a Winston-Lutz test. The CBCT image center was found to have excellent short-term positional repro-ducibility (i.e., less than 0.1 mm of wobble in each of the x (lateral), y (vertical), and z (longitudinal) directions) in 10 consecutive acquisitions. Measured over a seven-month period, the CBCT image center deviated from the radiation isocenter by 0.40 ± 0.12 mm (x), 0.43 ± 0.04 mm (y), and 0.34 ± 0.14 mm (z). The z displacement of the 3D CBCT image center was highly correlated (ρ = 0.997) with that of the 2D kV portal image center. The correlation coefficients in the x and y directions were poor (ρ = 0.66 and -0.35, respectively). Systematic discrepancies were found between the CBCT image center and the 2D MV, kV portal image centers. For the linear accelerator studied, we detected a 0.8 mm discrepancy between the CBCT image center and the MV EPID image center in the anterior-posterior direction.This discrepancy was demonstrated in a clinical case study where the patient was positioned with CBCT followed by MV portal verification. The results from the new QA procedure are useful for guiding high-precision patient positioning in stereotactic body radiation therapy.

Analytical calculation of central-axis dosimetric data for a dedicated 6-MV radiosurgery linear accelerator.

Narrow beams are extensively used in stereotactic radiosurgery. The accuracy of treatment planning dose calculation depends largely on how well the dosimetric data are measured during the machine commissioning. Narrow beams are characterized by the lack of lateral electronic equilibrium. The lateral electronic disequilibrium in the radiation field and detector's finite size are likely to compromise the accuracy in dose measurements in these beams. This may have a profound impact on outcome in patients who undergo stereotactic radiosurgery. To confirm the measured commissioning data for a dedicated 6-MV linear accelerator-based radiosurgery system, we developed an analytical model to calculate the narrow photon beam central-axis dose. This model is an extension of a previously reported method of Nizin and Mooij for the calculation of the absorbed dose under lateral electronic disequilibrium conditions at depth of dmax or greater. The scatter factor and tissue-maximum ratio were calculated for narrow beams using the parametrized model and compared to carefully measured results for the same beams. For narrow beam radii ranging from 0.2 to 1.5 cm, the differences between the analytical and measured scatter factors were no greater than 1.4%. In addition, the differences between the analytical and measured tissue-maximum ratios were within 3.3% for regions greater than the maximum dose depth. The estimated error of this analytical calculation was less than 2%, which is sufficient to validate measurement results.