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

Abstract

OBJECTIVEFunctional 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.METHODSThe 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/β) 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.RESULTSAfter 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.CONCLUSIONSUse 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.

Treatment Outcomes and Dose Rate Effects Following Gamma Knife Stereotactic Radiosurgery for Vestibular Schwannomas

“…Accordingly, dosimetric analyses for functional GKRS have demonstrated that predicted biologically effective doses for a given prescription dose vary widely across the lifespan of radioactive cobalt-60 sources. 57…”

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

“…For large‐volume GK institutions, it is not uncommon to treat patients with 10+ target sites, 19 which would further intensify the single PIV differences in overall treatment delivery time. In addition to reducing the clinical viability of a plan, there have been previous studies which have shown identical plans have been shown to produce lower biologically effective dose by 11.7% for GK deliveries as short as 30minute delivery times based upon intrafraction repair 18 . In other delivery sites, such as the prostate, the effects of intrafraction repair and source decay have been shown to reduce the BED by as much as 36% 20 …”

“…In the second dataset, this investigation demonstrated that using the 4 mm collimator shots to cover a 16 mm PIV resulted in a nearly unmanageable 130.3 min, compared with the 10.2 min when using a 16 mm collimator. Note that these times are scaled to a 3.5 Gy/min dose rate, which is only available immediately after source exchange, and some institutions operate until sources are around one half-life in age, 18 thus effectively doubling these delivery times.…”

“…Given that portions of the target will receive doses up to twice as high as the prescription dose, along with the versatility of the GK collimator delivery system, vastly different dose distributions can be generated depending on the planning team. This, in addition to dose ranges which are typically at least [15][16][17][18] Gy in a single fraction, [1][2][3] results in a persistent quest in GK treatment planning on identifying favorable dosimetric characteristics of GK plans that would produce the best tumor control is acheived. 4 Common plan quality indices such as the conformity index 1,5 or the Paddick index 6 are focused upon the shape and coverage of the prescription isodose.…”

Radiation repair models for clinical application

“…(1) External beam fractions of extended duration [22][23][24] (2) Some forms of pulsed brachytherapy [25][26][27] (3) Medium dose-rate brachytherapy 28 (4) Progressively extended treatment times in external beam 60 Co, Gamma Knife therapy or 192 Ir brachytherapy due to source decay. 29 (See also Jones and Hopewell in this Special Review).…”