Oliver Blanck

The design, physical properties and clinical utility of an iris collimator for robotic radiosurgery.

Robotic radiosurgery using more than one circular collimator can improve treatment plan quality and reduce total monitor units (MU). The rationale for an iris collimator that allows the field size to be varied during treatment delivery is to enable the benefits of multiple-field-size treatments to be realized with no increase in treatment time due to collimator exchange or multiple traversals of the robotic manipulator by allowing each beam to be delivered with any desired field size during a single traversal. This paper describes the Iris variable aperture collimator (Accuray Incorporated, Sunnyvale, CA, USA), which incorporates 12 tungsten-copper alloy segments in two banks of six. The banks are rotated by 30 degrees with respect to each other, which limits the radiation leakage between the collimator segments and produces a 12-sided polygonal treatment beam. The beam is approximately circular, with a root-mean-square (rms) deviation in the 50% dose radius of <0.8% (corresponding to <0.25 mm at the 60 mm field size) and an rms variation in the 20-80% penumbra width of about 0.1 mm at the 5 mm field size increasing to about 0.5 mm at 60 mm. The maximum measured collimator leakage dose rate was 0.07%. A commissioning method is described by which the average dose profile can be obtained from four profile measurements at each depth based on the periodicity of the isodose line variations with azimuthal angle. The penumbra of averaged profiles increased with field size and was typically 0.2-0.6 mm larger than that of an equivalent fixed circular collimator. The aperture reproducibility is < or =0.1 mm at the lower bank, diverging to < or =0.2 mm at a nominal treatment distance of 800 mm from the beam focus. Output factors (OFs) and tissue-phantom-ratio data are identical to those used for fixed collimators, except the OFs for the two smallest field sizes (5 and 7.5 mm) are considerably lower for the Iris Collimator. If average collimator profiles are used, the assumption of circular symmetry results in dose calculation errors that are <1 mm or <1% for single beams across the full range of field sizes; errors for multiple non-coplanar beam treatment plans are expected to be smaller. Treatment plans were generated for 19 cases using the Iris Collimator (12 field sizes) and also using one and three fixed collimators. The results of the treatment planning study demonstrate that the use of multiple field sizes achieves multiple plan quality improvements, including reduction of total MU, increase of target volume coverage and improvements in conformality and homogeneity compared with using a single field size for a large proportion of the cases studied. The Iris Collimator offers the potential to greatly increase the clinical application of multiple field sizes for robotic radiosurgery.

Local tumor control probability modeling of primary and secondary lung tumors in stereotactic body radiotherapy

BACKGROUND AND PURPOSE To evaluate whether local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) varies between lung metastases of different primary cancer sites and between primary non-small cell lung cancer (NSCLC) and secondary lung tumors. MATERIALS AND METHODS A retrospective multi-institutional (n=22) database of 399 patients with stage I NSCLC and 397 patients with 525 lung metastases was analyzed. Irradiation doses were converted to biologically effective doses (BED). Logistic regression was used for local tumor control probability (TCP) modeling and the second-order bias corrected Akaike Information Criterion was used for model comparison. RESULTS After median follow-up of 19 months and 16 months (n.s.), local tumor control was observed in 87.7% and 86.7% of the primary and secondary lung tumors (n.s.), respectively. A strong dose-response relationship was observed in the primary NSCLC and metastatic cohort but dose-response relationships were not significantly different: the TCD90 (dose to achieve 90% TCP; BED of maximum planning target volume dose) estimates were 176 Gy (151-223) and 160 Gy (123-237) (n.s.), respectively. The dose-response relationship was not influenced by the primary cancer site within the metastatic cohort. CONCLUSIONS Dose-response relationships for local tumor control in SBRT were not different between lung metastases of various primary cancer sites and between primary NSCLC and lung metastases.

A dosimetric comparison of real-time adaptive and non-adaptive radiotherapy: A multi-institutional study encompassing robotic, gimbaled, multileaf collimator and couch tracking.

Purpose A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion. Methods and materials Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for γ-tests recorded. Results For all lung traces all measurement sets show improved dose accuracy with a mean 2%/2 mm γ-fail rate of 1.6% with adaptation and 15.2% without adaptation (p < 0.001). For all prostate the mean 2%/2 mm γ-fail rate was 1.4% with adaptation and 17.3% without adaptation (p < 0.001). The difference between the four systems was small with an average 2%/2 mm γ-fail rate of <3% for all systems with adaptation for lung and prostate. Conclusions The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods.

Stereotactic body radiotherapy (SBRT) for medically inoperable lung metastases—A pooled analysis of the German working group “stereotactic radiotherapy”

OBJECTIVES The current literature on stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by small patient cohorts with heterogeneous primary tumors, metastases location and dose regimes. Hence, this study established a multi-institutional database of 700 patients treated with SBRT for pulmonary metastases to identify prognostic factors influencing survival and local control. MATERIALS AND METHODS All German radiotherapy departments were contacted and invited to participate in this analysis. A total number of 700 patients with medically inoperable lung metastases treated with SBRT in 20 centers between 1997 and 2014 were included in a database. Primary and metastatic tumor characteristics, treatment characteristics and follow-up data including survival, local control, distant metastases, and toxicity were evaluated. Lung metastases were treated with median PTV-encompassing single doses of 12.5Gy (range 3.0-33.0Gy) in a median number of 3 fractions (range 1-13). RESULTS After a median follow-up time of 14.3 months, 2-year local control (LC) and overall survival (OS) were 81.2% and 54.4%, respectively. In multivariate analysis, OS was most significantly influenced by pretreatment performance status, maximum metastasis diameter, primary tumor histology, time interval between primary tumor diagnosis and SBRT treatment and number of metastases. For LC, independent prognostic factors were pretreatment performance status, biological effective dose (BED) at PTV isocenter (BEDISO) and single fraction (PTV-encompassing) dose in multivariate analysis. Radiation-induced pneumonitis grade 2 or higher was observed in 6.5% of patients. The only factor significantly influencing toxicity was BEDISO (p=0.006). CONCLUSION SBRT for medically inoperable patients with pulmonary metastases achieved excellent local control and promising overall survival. Important prognostic factors were identified for selecting patients who might benefit most from this therapy approach.

A new correction method serving to eliminate the parabola effect of flatbed scanners used in radiochromic film dosimetry

PURPOSE The purpose of this study is the correction of the lateral scanner artifact, i.e., the effect that, on a large homogeneously exposed EBT3 film, a flatbed scanner measures different optical densities at different positions along the x axis, the axis parallel to the elongated light source. At constant dose, the measured optical density profiles along this axis have a parabolic shape with significant dose dependent curvature. Therefore, the effect is shortly called the parabola effect. The objective of the algorithm developed in this study is to correct for the parabola effect. Any optical density measured at given position x is transformed into the equivalent optical density c at the apex of the parabola and then converted into the corresponding dose via the calibration of c versus dose. METHODS For the present study EBT3 films and an Epson 10000XL scanner including transparency unit were used for the analysis of the parabola effect. The films were irradiated with 6 MV photons from an Elekta Synergy accelerator in a RW3 slab phantom. In order to quantify the effect, ten film pieces with doses graded from 0 to 20.9 Gy were sequentially scanned at eight positions along the x axis and at six positions along the z axis (the movement direction of the light source) both for the portrait and landscape film orientations. In order to test the effectiveness of the new correction algorithm, the dose profiles of an open square field and an IMRT plan were measured by EBT3 films and compared with ionization chamber and ionization chamber array measurement. RESULTS The parabola effect has been numerically studied over the whole measuring field of the Epson 10000XL scanner for doses up to 20.9 Gy and for both film orientations. The presented algorithm transforms any optical density at position x into the equivalent optical density that would be measured at the same dose at the apex of the parabola. This correction method has been validated up to doses of 5.2 Gy all over the scanner bed with 2D dose distributions of an open square photon field and an IMRT distribution. CONCLUSIONS The algorithm presented in this study quantifies and corrects the parabola effect of EBT3 films scanned in commonly used commercial flatbed scanners at doses up to 5.2 Gy. It is easy to implement, and no additional work steps are necessary in daily routine film dosimetry.

Stereotactic body radiotherapy for oligo-metastatic liver disease – Influence of pre-treatment chemotherapy and histology on local tumor control

INTRODUCTION Stereotactic body radiation therapy (SBRT) is applied in the oligometastatic setting to treat liver metastases. However, factors influencing tumor control probability (TCP) other than radiation dose have not been thoroughly investigated. Here we set out to investigate such factors with a focus on the influence of histology and chemotherapy prior to SBRT using a large multi-center database from the German Society of Radiation Oncology. METHODS 452 SBRT treatments in 363 patients were analyzed after collection of patient, tumor and treatment data in a multi-center database. Histology was considered through random effects in semi-parametric and parametric frailty models. Dose prescriptions were parametrized by conversion to the maximum biologically effective dose using alpha/beta of 10Gy (BEDmax). RESULTS After adjusting for histology, BEDmax was the strongest predictor of TCP. Larger PTV volumes, chemotherapy prior to SBRT and simple motion management techniques predicted significantly lower TCP. The model predicted a BED of 209±67Gy10 necessary for 90% TCP at 2years with no prior chemotherapy, but 286±78Gy10 when chemotherapy had been given. Breast cancer metastases were significantly more responsive to SBRT compared to other histologies with 90% TCP at 2years achievable with BEDmax of 157±80Gy10 or 80±62Gy10 with and without prior chemotherapy, respectively. CONCLUSIONS Besides dose, histology and pretreatment chemotherapy were important factors influencing local TCP in this large cohort of liver metastases. After adjusting for prior chemotherapy, our data add to the emerging evidence that breast cancer metastases do respond better to hypofractionated SBRT compared to other histologies.

Dose-Escalation Study for Cardiac Radiosurgery in a Porcine Model

PURPOSE To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. METHODS AND MATERIALS Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm(3)). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. RESULTS Transmural scarring of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. CONCLUSIONS Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.

Real time tracking in liver SBRT: comparison of CyberKnife and Vero by planning structure-based γ-evaluation and dose-area-histograms.

The purpose of this study was to evaluate and compare two clinical tracking systems for radiosurgery with regard to their dosimetric and geometrical accuracy in liver SBRT: the robot-based CyberKnife and the gimbal-based Vero. Both systems perform real-time tumour tracking by correlating internal tumour and external surrogate motion. CyberKnife treatment plans were delivered to a high resolution 2D detector array mounted on a 4D motion platform, with the platform simulating (a) tumour motion trajectories extracted from the corresponding CyberKnife predictor log files and (b) the tumour motion trajectories with superimposed baseline-drift. Static reference and tracked dose measurements were compared and dosimetric as well as geometrical uncertainties analyzed by a planning structure-based evaluation. For (a), γ-passing rates inside the CTV (γ-criteria of 1% / 1 mm) ranged from 95% to 100% (CyberKnife) and 98% to 100% (Vero). However, dosimetric accuracy decreases in the presence of the baseline-drift. γ-passing rates for (b) ranged from 26% to 92% and 94% to 99%, respectively; i.e. the effect was more pronounced for CyberKnife. In contrast, the Vero system led to maximum dose deviations in the OAR between  +1.5 Gy to +6.0 Gy (CyberKnife: +0.5 Gy to +3.5 Gy). Potential dose shifts were interpreted as motion-induced geometrical tracking errors. Maximum observed shift ranges were  -1.0 mm to  +0.7 mm (lateral) /-0.6 mm to +0.1 mm (superior-inferior) for CyberKnife and  -0.8 mm to +0.2 mm /-0.8 mm to +0.4 mm for Vero. These values illustrate that CyberKnife and Vero provide high precision tracking of regular breathing patterns. Even for the modified motion trajectory, the obtained dose distributions appear to be clinical acceptable with regard to literature QA γ-criteria of 3% / 3 mm.

A comparison of two clinical correlation models used for real-time tumor tracking of semi-periodic motion: A focus on geometrical accuracy in lung and liver cancer patients.

PURPOSE A head-to-head comparison of two clinical correlation models with a focus on geometrical accuracy for internal tumor motion estimation during real-time tumor tracking (RTTT). METHODS AND MATERIALS Both the CyberKnife (CK) and the Vero systems perform RTTT with a correlation model that is able to describe hysteresis in the breathing motion. The CK dual-quadratic (DQ) model consists of two polynomial functions describing the trajectory of the tumor for inhale and exhale breathing motion, respectively. The Vero model is based on a two-dimensional (2D) function depending on position and speed of the external breathing signal to describe a closed-loop tumor trajectory. In this study, 20 s of internal motion data, using an 11 Hz (on average) full fluoroscopy (FF) sequence, was used for training of the CK and Vero models. Further, a subsampled set of 15 internal tumor positions (15p) equally spread over the different phases of the breathing motion was used for separate training of the CK DQ model. Also a linear model was trained using 15p and FF tumor motion data. Fifteen liver and lung cancer patients, treated on the Vero system with RTTT, were retrospectively evaluated comparing the CK FF, CK 15p and Vero FF models using an in-house developed simulator. The distance between estimated target position and the tumor position localized by X-ray imaging was measured in the beams-eye view (BEV) to calculate the 95th percentile BEV modeling errors (ME(95,BEV)). Additionally, the percentage of ME(95,BEV) smaller than 5 mm (P(5mm)) was determined for all correlation models. RESULTS In general, no significant difference (p>0.05, paired t-test) was found between the CK FF and Vero models. Based on patient-specific evaluation of the geometrical accuracy of the linear, CK DQ and Vero correlation models, no statistical necessity (p>0.05, two-way ANOVA) of including hysteresis in correlation models was proven, although during inhale breathing motion, the linear model resulted in a decreased P(5mm) with 5-6% compared to both the DQ CK and Vero models. CONCLUSION Dual-quadratic CyberKnife and 2D Vero correlation models were interchangeable in terms of geometrical accuracy with the CK linear ME(95,BEV)=4.1 mm, CK dual-quadratic ME(95,BEV)=3.9 mm and Vero ME(95,BEV)=3.7 mm, when modeled with FF sequence. CK DQ modeling based on 15p acquired in 20 s may lead to problems for internal motion estimation.

Film-based delivery quality assurance for robotic radiosurgery: Commissioning and validation

PURPOSE Robotic radiosurgery demands comprehensive delivery quality assurance (DQA), but guidelines for commissioning of the DQA method is missing. We investigated the stability and sensitivity of our film-based DQA method with various test scenarios and routine patient plans. We also investigated the applicability of tight distance-to-agreement (DTA) Gamma-Index criteria. METHODS AND MATERIAL We used radiochromic films with multichannel film dosimetry and re-calibration and our analysis was performed in four steps: 1) Film-to-plan registration, 2) Standard Gamma-Index criteria evaluation (local-pixel-dose-difference ≤2%, distance-to-agreement ≤2 mm, pass-rate ≥90%), 3) Dose distribution shift until maximum pass-rate (Maxγ) was found (shift acceptance <1 mm), and 4) Final evaluation with tight DTA criteria (≤1 mm). Test scenarios consisted of purposefully introduced phantom misalignments, dose miscalibrations, and undelivered MU. Initial method evaluation was done on 30 clinical plans. RESULTS Our method showed similar sensitivity compared to the standard End-2-End-Test and incorporated an estimate of global system offsets in the analysis. The simulated errors (phantom shifts, global robot misalignment, undelivered MU) were detected by our method while standard Gamma-Index criteria often did not reveal these deviations. Dose miscalibration was not detected by film alone, hence simultaneous ion-chamber measurement for film calibration is strongly recommended. 83% of the clinical patient plans were within our tight DTA tolerances. CONCLUSION Our presented methods provide additional measurements and quality references for film-based DQA enabling more sensitive error detection. We provided various test scenarios for commissioning of robotic radiosurgery DQA and demonstrated the necessity to use tight DTA criteria.