Evaluation of Elekta Agility multi-leaf collimator performance using statistical process control tools.

PURPOSE: To evaluate the performance and stability of Elekta Agility multi-leaf collimator (MLC) leaf positioning using a daily, automated quality control (QC) test based on megavoltage (MV) images in combination with statistical process control tools, and identify special causes of variations in performance. METHODS: Leaf positions were collected daily for 13 Elekta linear accelerators over 11-37 months using the automated QC test, which analyzes 23 MV images to determine the location of MLC leaves relative to radiation isocenter. Leaf positioning stability was assessed using individual and moving range control charts. Specification levels of ±0.5, ±1, and ±1.5 mm were tested to determine positional accuracy. The durations between out-of-control and out-of-specification events were determined. Peaks in out-of-control leaf positions were identified and correlated to servicing events recorded for the whole duration of data collection. RESULTS: Mean leaf position error was -0.01 mm (range -1.3-1.6). Data stayed within ±1 mm specification for 457 days on average (range 3-838) and within ±1.5 mm for the entire date range. Measurements stayed within ±0.5 mm for 1 day on average (range 0-17); however, our MLC leaves were not calibrated to this level of accuracy. Leaf position varied little over time, as confirmed by tight individual (mean ±0.19 mm, range 0.09-0.43) and moving range (mean 0.23 mm, range 0.10-0.53) control limits. Due to sporadic out-of-control events, the mean in-control duration was 2.8 days (range 1-28.5). A number of factors were found to contribute to leaf position errors and out-of-control behavior, including servicing events, beam spot motion, and image artifacts. CONCLUSIONS: The Elekta Agility MLC model was found to perform with high stability, as evidenced by the tight control limits. The in-specification durations support the current recommendation of monthly MLC QC tests with a ±1 mm tolerance. Future work is on-going to determine if performance can be optimized further using high-frequency QC test results to drive recalibration frequency.

Under conditions of large geometric miss, tumor control probability can be higher for static gantry intensity-modulated radiation therapy compared to volume-modulated arc therapy for prostate cancer.

The purpose of this work was to compare static gantry intensity-modulated radiation therapy (IMRT) with volume-modulated arc therapy (VMAT) in terms of tumor control probability (TCP) under scenarios involving large geometric misses, i.e., those beyond what are accounted for when margin expansion is determined. Using a planning approach typical for these treatments, a linear-quadratic-based model for TCP was used to compare mean TCP values for a population of patients who experiences a geometric miss (i.e., systematic and random shifts of the clinical target volume within the planning target dose distribution). A Monte Carlo approach was used to account for the different biological sensitivities of a population of patients. Interestingly, for errors consisting of coplanar systematic target volume offsets and three-dimensional random offsets, static gantry IMRT appears to offer an advantage over VMAT in that larger shift errors are tolerated for the same mean TCP. For example, under the conditions simulated, erroneous systematic shifts of 15mm directly between or directly into static gantry IMRT fields result in mean TCP values between 96% and 98%, whereas the same errors on VMAT plans result in mean TCP values between 45% and 74%. Random geometric shifts of the target volume were characterized using normal distributions in each Cartesian dimension. When the standard deviations were doubled from those values assumed in the derivation of the treatment margins, our model showed a 7% drop in mean TCP for the static gantry IMRT plans but a 20% drop in TCP for the VMAT plans. Although adding a margin for error to a clinical target volume is perhaps the best approach to account for expected geometric misses, this work suggests that static gantry IMRT may offer a treatment that is more tolerant to geometric miss errors than VMAT.

The relative biological effectiveness of out-of-field dose.

PURPOSE: using simulations and models derived from existing literature, this work investigates relative biological effectiveness (RBE) for out-of-field radiation and attempts to quantify the relative magnitudes of different contributing phenomena (spectral, bystander, and low dose hypersensitivity effects). Specific attention is paid to external beam radiotherapy treatments for prostate cancer. MATERIALS AND METHODS: using different biological models that account for spectral, bystander, and low dose hypersensitivity effects, the RBE was calculated for different points moving radially out from isocentre for a typical single arc VMAT prostate case. The RBE was found by taking the ratio of the equivalent dose with the physical dose. Equivalent doses were calculated by determining what physical dose would be necessary to produce the same overall biological effect as that predicted using the different biological models. RESULTS: spectral effects changed the RBE out-of-field less than 2%, whereas response models incorporating low dose hypersensitivity and bystander effects resulted in a much more profound change of the RBE for out-of-field doses. The bystander effect had the largest RBE for points located just outside the edge of the primary radiation beam in the cranial caudal (z-direction) compared to low dose hypersensitivity and spectral effects. In the coplanar direction, bystander effect played the largest role in enhancing the RBE for points up to 8.75 cm from isocentre. CONCLUSIONS: spectral, bystander, and low dose hypersensitivity effects can all increase the RBE for out-of-field radiation doses. In most cases, bystander effects seem to play the largest role followed by low dose hypersensitivity. Spectral effects were unlikely to be of any clinical significance. Bystander, low dose hypersensitivity, and spectral effect increased the RBE much more in the cranial caudal direction (z-direction) compared with the coplanar directions.

Potential implications of the bystander effect on TCP and EUD when considering target volume dose heterogeneity.

PURPOSE: In light of in vitro evidence suggesting that radiation-induced bystander effects may enhance non-local cell killing, there is potential for impact on radiotherapy treatment planning paradigms such as the goal of delivering a uniform dose throughout the clinical target volume (CTV). This work applies a bystander effect model to calculate equivalent uniform dose (EUD) and tumor control probability (TCP) for external beam prostate treatment and compares the results with a more common model where local response is dictated exclusively by local absorbed dose. The broad assumptions applied in the bystander effect model are intended to place an upper limit on the extent of the results in a clinical context. MATERIALS AND METHODS: EUD and TCP of a prostate cancer target volume under conditions of increasing dose heterogeneity were calculated using two models: One incorporating bystander effects derived from previously published in vitro bystander data ( McMahon et al. 2012 , 2013a); and one using a common linear-quadratic (LQ) response that relies exclusively on local absorbed dose. Dose through the CTV was modelled as a normal distribution, where the degree of heterogeneity was then dictated by changing the standard deviation (SD). Also, a representative clinical dose distribution was examined as cold (low dose) sub-volumes were systematically introduced. RESULTS: The bystander model suggests a moderate degree of dose heterogeneity throughout a target volume will yield as good or better outcome compared to a uniform dose in terms of EUD and TCP. For a typical intermediate risk prostate prescription of 78 Gy over 39 fractions maxima in EUD and TCP as a function of increasing SD occurred at SD ∼ 5 Gy. The plots only dropped below the uniform dose values for SD ∼ 10 Gy, almost 13% of the prescribed dose. Small, but potentially significant differences in the outcome metrics between the models were identified in the clinically-derived dose distribution as cold sub-volumes were introduced. CONCLUSIONS: In terms of EUD and TCP, the bystander model demonstrates the potential to deviate from the common local LQ model predictions as dose heterogeneity through a prostate CTV varies. The results suggest, at least in a limiting sense, the potential for allowing some degree of dose heterogeneity within a CTV, although further investigation of the assumptions of the bystander model are warranted.

Potential implications on TCP for external beam prostate cancer treatment when considering the bystander effect in partial exposure scenarios.

PURPOSE: This work investigated the potential implications on tumour control probability (TCP) for external beam prostate cancer treatment when considering the bystander effect in partial exposure scenarios. MATERIALS AND METHODS: The biological response of a prostate cancer target volume under conditions where a sub-volume of the target volume was not directly irradiated was modelled in terms of surviving fraction (SF) and Poisson-based TCP. A direct comparison was made between the linear-quadratic (LQ) response model, and a response model that incorporates bystander effects as derived from published in vitro data by McMahon et al. in 2012 and 2013. Scenarios of random and systematic misses were considered. RESULTS: Our results suggested the potential for the bystander effect to deviate from LQ predictions when even very small (< 1%) sub-volumes of the target volume were directly irradiated. Under conditions of random misses for each fraction, the bystander model predicts a 3% and 1% improvement in tumour control compared to that predicted by an LQ model when only 90% and 95% of the prostate cells randomly receive the intended dose. Under conditions of systematic miss, if even a small portion of the target volume is not directly exposed, the LQ model predicts a TCP approaching zero, whereas the bystander model suggests TCP will improve starting at exposed volumes of around 85%. CONCLUSIONS: The bystander model, when applied to clinically relevant scenarios, demonstrates the potential to deviate from the TCP predictions of the common local LQ model when sub-volumes of a target volume are randomly or systematically missed over a course of fractionated radiation therapy.