Associating dose-volume characteristics with theoretical radiobiological metrics for rapid Gamma Knife stereotactic radiosurgery plan evaluation.

PURPOSE: To examine general dose-volume characteristics in Gamma Knife (GK) plans which may be associated with higher tumor control probability (TCP) and equivalent uniform dose (EUD) using characteristic curve sets. METHODS: Two sets of dose-volume histograms (DVHs) were exported alongside an analytical purpose-generated DVH: (a) single-shot large collimator (8 or 16 mm) emulated with multiple shots of 4 mm collimator. (b) shot-within-shot (SWS) technique with isodose lines (IDLs) of 40-75%. TCP, average dose, EUD in single-fraction (EUDT ) and 2 Gy fractionated regimens (EUDR ) were examined for trends with cumulative DVH (cDVH) shape as calculated using a linear-quadratic cell survival model (α/ß = 10.0 Gy, N0  = 1 × 106 ) with both α = 0.20 Gy-1 and α = 0.23 Gy-1 . RESULTS: Using α = 0.20 Gy-1 (α = 0.23 Gy-1 ), plans in the analytical set with higher shoulder regions had TCP, EUDT , EUDR increased by 180%, 5.9%, 10.7% (11.2%, 6.3%, 10.0%), respectively. With α = 0.20 Gy-1 (α = 0.23 Gy-1 ), plans with higher heels had TCP, EUDT , EUDR increased by 4.0%, <1%, <1% (0.6%, <1%, <1%), respectively. In emulating a 16 (8) mm collimator, 64 (12) shots of the small collimators were used. Plans based on small collimators had higher shoulder regions and, with α = 0.20 Gy-1 (α = 0.23 Gy-1 ), TCP, EUDT , EUDR was increased up to 351.4%, 5.0%, 8.8% (270.4%, 5.0%, 6.8%) compared with the single-shot large collimator. Delivery times ranged from 10.2 to 130.3 min. The SWS technique used 16:8 mm collimator weightings ranging from 1:2 to 9.2:1 for 40-75% IDL. With α = 0.20 Gy-1 (α = 0.23 Gy-1 ), the 40% IDL plan had the highest shoulder with increased TCP, EUDT , EUDR by 130.7%, 9.6%, 17.1% (12.9%, 9.1%, 16.4%) over the 75% IDL plan. Delivery times ranged 6.9-13.8 min. CONCLUSIONS: The magnitude of the shoulder region characteristic to GK cDVHs may be used to rapidly identify superior plan among candidates. Practical issues such as delivery time may require further consideration.

The impact of cobalt-60 source age on biologically effective dose in high-dose functional Gamma Knife radiosurgery.

OBJECTIVE Functional Gamma Knife radiosurgery (GKRS) procedures have been increasingly used for treating patients with tremor, trigeminal neuralgia (TN), and refractory obsessive-compulsive disorder. Although its rates of toxicity are low, GKRS has been associated with some, if low, risks for serious sequelae, including hemiparesis and even death. Anecdotal reports have suggested that even with a standardized prescription dose, rates of functional GKRS toxicity increase after replacement of an old cobalt-60 source with a new source. Dose rate changes over the course of the useful lifespan of cobalt-60 are not routinely considered in the study of patients treated with functional GKRS, but these changes may be associated with significant variation in the biologically effective dose (BED) delivered to neural tissue. METHODS The authors constructed a linear-quadratic model of BED in functional GKRS with a dose-protraction factor to correct for intrafraction DNA-damage repair and used standard single-fraction doses for trigeminal nerve ablation for TN (85 Gy), thalamotomy for tremor (130 Gy), and capsulotomy for obsessive-compulsive disorder (180 Gy). Dose rate and treatment time for functional GKRS involving 4-mm collimators were derived from calibrations in the authors' department and from the cobalt-60 decay rate. Biologically plausible values for the ratio for radiosensitivity to fraction size (α/ß) and double-strand break (DSB) DNA repair halftimes (τ) were estimated from published experimental data. The biphasic characteristics of DSB repair in normal tissue were accounted for in deriving an effective τ1 halftime (fast repair) and τ2 halftime (slow repair). A sensitivity analysis was performed with a range of plausible parameter values. RESULTS After replacement of the cobalt-60 source, the functional GKRS dose rate rose from 1.48 to 2.99 Gy/min, treatment time fell, and estimated BED increased. Assuming the most biologically plausible parameters, source replacement resulted in an immediate relative BED increase of 11.7% for GKRS-based TN management with 85 Gy, 15.6% for thalamotomy with 130 Gy, and 18.6% for capsulotomy with 180 Gy. Over the course of the 63-month lifespan of the cobalt-60 source, BED decreased annually by 2.2% for TN management, 3.0% for thalamotomy, and 3.5% for capsulotomy. CONCLUSIONS Use of a new cobalt-60 source after replacement of an old source substantially increases the predicted BED for functional GKRS treatments for the same physical dose prescription. Source age, dose rate, and treatment time should be considered in the study of outcomes after high-dose functional GKRS treatments. Animal and clinical studies are needed to determine how this potential change in BED contributes to GKRS toxicity and whether technical adjustments should be made to reduce dose rates or prescription doses with newer cobalt-60 sources.

Comparison of an image registration technique based on normalized mutual information with a standard method utilizing implanted markers in the staged radiosurgical treatment of large arteriovenous malformations.

PURPOSE: To compare a noninvasive technique based on normalized mutual information for registering image sets associated with staged radiosurgical treatments of large arteriovenous malformations (AVMs), with a gold-standard method using radiographically evident markers implanted in the skull. METHODS: Nine patients receiving multistage treatment of large AVMs at the University of California at San Francisco (UCSF) gamma knife facility were included in this study. For each patient, the transformations of shot coordinates between a reference treatment stage and subsequent treatment stages were determined at UCSF, based on radiographically defined coordinates of implanted markers in each stereotactic space. A magnetic resonance (MR) image set was acquired for each treatment stage, and used for treatment planning. The two MR image sets for each treatment pair were sent to Yale for an unbiased, independent analysis of shot transformations. An image registration technique based on normalized mutual information was used to produce a single fused image study for each treatment pair. External copper sulfate fiducial markers for both image sets were evident on the fused images, allowing coordinates in both stereotactic systems to be defined. Coordinate transformation between the two systems was determined, based on digitized coordinates of seven common fiducial marker images. RESULTS: The average measured overall root-mean-square discrepancy between the Yale and UCSF transformed shot coordinates is 1.1 +/- 0.3 mm. The corresponding error in Yale transformed coordinates is 1.0 +/- 0.3 mm, assuming an inherent 0.5 mm error in the UCSF method. CONCLUSIONS: The normalized mutual information method can be used to obtain good image registration between successive sessions in staged treatments. Further improvements in the reported methodology are outlined. Because the mutual information method is less invasive than the implanted marker method, it may be preferable in many cases.

A technique to re-establish dose distributions for previously treated brain cancer patients in external beam radiotherapy.

Tumor recurrences or new tumors may develop after irradiation of local lesion(s) in the brain, and additional radiotherapy treatments are often needed for previously treated patients. It is critical to re-establish the dose distributions delivered during the previous treatment in the current patient geometry, so that the previous dose distributions can be accurately taken into consideration in the design of the current treatment plan. The difficulty in re-establishing the previous treatment dose distributions in the current patient geometry arises from the fact that the patient position at the time of reirradiation is different from that at the previous treatment session. Simple re-entry of the previous isocenter coordinates, gantry, and couch and collimator angles into the new treatment plan would result in incorrect beam orientations relative to the new patient anatomy, and therefore incorrect display of the previous dose distributions on the current patient anatomy. To address this issue, a method has been developed so that the previous dose distributions can be accurately re-established in the framework of the current brain treatment. The method involves 3 matrix transformations: (1) transformation of beams from machine coordinate system to patient coordinate system in the previous treatment; (2) transformation of beams from patient coordinate system in the previous treatment to patient coordinate system in the current treatment; and (3) transformation of beams from patient coordinate system in the current treatment to machine coordinate system. The transformation matrices used in the second transformation are determined by registration using a mutual information-based algorithm with which the old and new computed tomography (CT) scan sets are registered automatically without human interpretation. A series of transformation matrices are derived to calculate the isocenter coordinates, the gantry, couch, and collimator angles of the beams for the previous treatment in the current patient geometry, and the previous dose distributions are re-established on the current CT images. The method has been proven to be successful and robust.