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The capability of the TrueBeam treatment system to deliver step and shoot IMRT plans at low dose rates was evaluated. Beam characteristics during low dose rates (5 to 100 MU/min) were evaluated for consistency using a planar ion chamber array. MU constancy, linearity, and beam profile symmetry were all found to be equivalent within 0.5%. The response of the Scandi Dos Delta 4 system was also evaluated at low dose rates of using static open beams compared to ion chamber measurements, and step and shoot IMRT plans comparing 5 - 20 MU/min and 100 MU/min dose rates, with a maximum observed absolute dose difference of 0.8% and equivalence margin of 0.2%. The Gamma Index and measurement reproducibility were also found to be equivalent.

Pulsed reduced dose-rate radiotherapy (PRDR) has become a powerful treatment for recurrent diseases, which comprise approximately 15% - 20% of treatments [

Due to the complex nature of these treatments, PRDR using 3D-conformal techniques can be very difficult. Often patients have been previously irradiated; as such, nearby critical structures may have already received at or close to their toxicity limit. Researchers are actively investigating ways to apply PRDR to more advanced techniques, such as static field Intensity Modulated Radiation Therapy (IMRT) [

When delivering PRDR treatments on the Varian^{®} TrueBeam™ system (Varian Medical Systems, Palo Alto, CA), an alternative technique can be used to reduce the time averaged dose rate. Instead of splitting the total dose into 0.2 Gy pulses, a lower repetition rate can be used to achieve a time averaged dose rate of 0.0667 Gy/min. The TrueBeam system can run as low as 5 MU/min. This greatly simplifies treatment planning of PRDR cases, as conventional (normal fractionation) beam arrangements and optimization techniques can be used. After optimization, the dose from each beam to the target can be computed and the dose rate adjusted during treatment delivery to achieve the desired target dose rate.

For VMAT and sliding window IMRT techniques, reducing the repetition rate will significantly slow down the gantry and MLC leaf motion, respectively. Even with static field step and shoot-type plans, the low repetition rate may affect the operation of the servo mechanisms that maintain beam stability parameters such as flatness, symmetry, and dose per MU. Typical IMRT commissioning practices also may not specifically include testing delivery at these low repetition rates [

Furthermore, performing patient specific plan delivery Quality Assurance (QA) at such a low repetition rate can also be problematic. Jursinic et al. [^{®} ArcCHECK^{®} measurement phantom (Sun Nuclear Corporation, Melbourne FL), finding that the ArcCHECK under-responded by −2.2% relative to ion chamber measurements at 5 MU/min. This adds additional challenges when commissioning a PRDR program; prior to performing end-to-end testing on an IMRT QA phantom, users must first re-validate their QA system at these repetition rates and factor their devices’ limitations into their results.

After commissioning is completed, there is an additional logistical concern as well. Conducting PRDR IMRT delivery QA measurements at the true low dose rate requires at least 30 minutes per run. Plans often require more than one measurement as well (either for troubleshooting or to increase the detector spatial frequency/area), making it difficult to conduct these measurements after hours in a busy clinic.

The purpose of this study was to demonstrate a procedure by which other clinicians could follow to develop PRDR at their clinics. The procedure starts with a series of tests to validate the delivery system at low repetition rates, then to characterize the performance of the IMRT QA system, and finally a series of end-to-end tests of patient plans that establish equivalence between IMRT delivery at PRDR and conventional repetition rates. To the author’s knowledge, this is also the first reported characterization of the ScandiDos Delta4^{®} phantom (ScandiDos AB, Uppsala Sweden) at low repetition rates.

All measurements were performed on the TrueBeam 2.5 treatment system using the conventional flattened 6 MV beam. IMRT QA phantom measurements were acquired on the Delta4 phantom and October 2016 software. Where stated that measurements were performed at each dose rate, acquisitions were repeated at 5, 10, 15, 20, 40, 60, 80, 100, and 600 MU/min. Unless otherwise noted, static beams were delivered using a 20 × 20 cm^{2} open field, IEC 0˚ gantry/collimator positions, with the device set up to 100 cm Source to Surface Distance (SSD) using the optical distance indicator and aligned to the treatment system central axis using the light field, verified by the lasers.

Monitor unit dose, linearity, and beam flatness/symmetry reproducibility with dose rate were evaluated using the Sun Nuclear IC Profiler™ device and v3.4.2 software. The IC Profiler was chosen as it has been previously demonstrated to be equivalent to water tank measurements detecting changes in these metrics [

The area symmetry

The diagonal flatness

The symmetry and flatness statistics from 5 to 100 MU/min tested were tested for equivalence to their respective 600 MU/min values using a paired Two One-Sided Test (TOST) by Schuirmann [

Next, an IBA FC65-P Farmer chamber (Ion Beam Applications SA, Louvain-la-Neuve Belgium) was placed at 1.5 cm depth in solid water. The chamber was then connected to a Standard Imaging^{®} SuperMax electrometer (Standard Imaging Inc., Middleton, WI). The collected charge was recorded for 5, 10, 15, 25, and 50 MU delivery using a 20 × 20 cm^{2} open field, 0˚ gantry, and 5 MU/min dose rate and corrected for temperature and pressure. The MU linearity residual errors were computed as the observed relative corrected charge minus the predicted value given a linear fit through 50 MU. The standard error was computed as the root mean square of all residuals.

Delta 4 response reproducibility with dose rate was evaluated by comparing the Delta 4 response relative to an ionization chamber. Using the same ionization chamber setup as before, the collected charge was recorded for 50 MU at each dose rate. The measurements were then repeated with the Delta 4 aligned to isocenter. For each measurement, mean dose across the central 6 × 6 cm^{2} detectors was recorded and divided by the ionization chamber response. The ratios were then normalized to 600 MU/min and tested for equivalence and linear dependence as before using a 0.2% equivalence margin. Verification of MU linearity was also repeated with the Delta 4.

To validate the equivalence of Delta 4 IMRT QA results with dose rate, three PRDR static step and shoot IMRT QA plans were delivered at low dose rates and 100 MU/min. Each plan was optimized in the Pinnacle^{3} v9.8 Treatment Planning System (Philips Healthcare, Madison, WI). A summary of the beams in each plan are provided in ^{3}. The average number of MU per segment ranged from 3.1 to 12.3, with a mean of 4.7 MU. Dose rate ranged from 5 to 20 MU/min.

Next, each plan was copied to the Delta 4 and re-calculated using a 2 × 2 × 2 mm^{3} resolution. Each plan was then delivered to the Delta 4 at the low dose rate and at 100 MU/min and analyzed in the Delta 4 software. The right parietal lobe plan was measured both 5 MU/min and 10 MU/min to provide additional statistical power. The median absolute dose in the target region defined by diodes above 50% of the maximum dose and mean Gamma index [

Area Treated | Beam | Gantry | Field Size | CPs | MU | Dose Rate |
---|---|---|---|---|---|---|

Anterior brain | 01 Vertex | 140˚ | 14.5 × 13.0 cm^{2 } | 13 | 74 | 20 MU/min |

02 LAO | 55˚ | 14.0 × 14.5 cm^{2} | 10 | 74 | 10 MU/min | |

03 LPO1 | 100˚ | 14.5 × 14.0 cm^{2} | 11 | 117 | 10 MU/min | |

04 LPO2 | 135˚ | 10.0 × 14.5 cm^{2} | 11 | 39 | 15 MU/min | |

05 PA | 180˚ | 13.0 × 14.0 cm^{2} | 12 | 41 | 20 MU/min | |

06 RPO1 | 220˚ | 13.5 × 14.0 cm^{2} | 11 | 41 | 15 MU/min | |

07 RPO2 | 260˚ | 12.9 × 14.0 cm^{2} | 15 | 104 | 15 MU/min | |

08 RAO | 300˚ | 14.5 × 13.5 cm^{2} | 6 | 74 | 20 MU/min | |

Vertex brain | 01 RPO | 225˚ | 7.5 × 5.0 cm^{2} | 8 | 59 | 10 MU/min |

02 RAO | 290˚ | 7.0 × 5.0 cm^{2} | 8 | 66 | 10 MU/min | |

03 LAO | 70˚ | 7.5 × 5.0 cm^{2} | 10 | 62 | 5 MU/min | |

04 LPO | 140˚ | 7.5 × 5.0 cm^{2} | 8 | 56 | 5 MU/min | |

05 Vertex | 41˚ | 5.5 × 5.0 cm^{2} | 7 | 57 | 5 MU/min | |

Right parietal lobe | 01 PA | 180˚ | 11.0 × 13.5 cm^{2} | 9 | 39 | 5, 10 MU/min |

02 RPO | 220˚ | 13.0 × 14.0 cm^{2} | 9 | 26 | 5, 10 MU/min | |

03 RLat | 270˚ | 13.0 × 15.0 cm^{2} | 7 | 24 | 5, 10 MU/min | |

04 RAO | 310˚ | 13.0 × 13.5 cm^{2} | 8 | 30 | 5, 10 MU/min | |

05 Vertex | 25˚ | 11.0 × 12.5 cm^{2} | 8 | 25 | 5, 10 MU/min |

Finally, to evaluate if dose rate affects the variance in IMRT QA results the right parietal lobe field 5 MU/min, 10 MU/min, and 100 MU/min beam measurements were each repeated three times. The standard deviation of each measurement set was then computed and tested for equivalence using the same paired TOST.

The following sections detail the results of the tests described above. Statistical analysis was conducted in R v.3.3.2 (R Foundation, https://www.r-project.org). A significance level of 0.05 (95% confidence) was established a priori for hypothesis testing.

^{2} = 0.73. This is likely due to the increased noise in the measured profiles as the dose rate decreased; the Y axis profile at 5 MU/min is plotted (in magenta) over the other dose rate profiles in

Area symmetry along the X axis was equivalent, ε = 0.5%, 95% CI [−0.37% 0.08%], p = 0.009, although with an inverse linear relationship with dose rate, p = 0.020, adj. R^{2} = 0.58. Area symmetry along the Y axis was equivalent, ε = 0.5%, 95% CI [0.22% 0.45%], p = 0.014, with no statistical linear dependence, p = 0.972.

Changes in symmetry with dose rate suggest that the dose servos have a slight effect on beam steering. That said, AAPM Task Group 142 [

^{2} de-

tectors) relative to ion chamber response under the same conditions as a function of dose rate, normalized to 1.000 at 600 MU/min. The low dose rates (5 - 100 MU/min) were found to be equivalent to 600 MU/min, ε = 0.2%, 95% CI [−0.20% −0.03%], p = 0.049, as well as no linear dependence with dose rate, p = 0.763.

These findings suggest that the Delta4 diode design does not suffer from the low dose rate under-response reported with the ArcCHECK [

Paired measurements (at 5 - 20 MU/min and 100 MU/min) of each beam in ^{2} = 0.99.

Furthermore, the variance in measurement was also found to be equivalent between dose rate groups (n = 5) for the median absolute dose, ε = 0.2%, 95% CI [−0.0056% 0.080%], p < 0.001, and Gamma index metrics, ε = 0.05, 95% CI [−0.0084 0.025], p = 0.003.

Finally, using the planned low dose rate, the composite median dose difference (between measured and calculated by the treatment planning system) in the target region and 3% (of maximum dose), 3 mm, 20% threshold Gamma index met the clinic’s IMRT QA acceptance criteria for all plans. The mean, minimum, and maximum median dose differences were 1.4%, 0.9%, and 2.2%, while the Gamma index pass rates were 99.3%, 98.2%, and 100%, respectively. It is notable that all PRDR plans yielded a median difference greater than one; unfortunately, not enough plans were measured to determine if the distribution of PRDR plan results statistically differ from other types of treatments. As this technique is employed at this center and more plans are created, this is an opportunity for future study.

This report demonstrates the capability of the TrueBeam system to deliver step and shoot PRDR IMRT plans and establishes equivalence between IMRT QA at 100 MU/min and lower dose rates. Static beam measurements found the TrueBeam system to achieve MU constancy, linearity, and symmetry within 0.5% margin. The Delta 4 phantom also responded equivalently within a 0.2% margin between ion chamber measurements for static beams and between 100 MU/min and lower dose rates for step and shoot IMRT.

Geurts, M. (2017) TrueBeam Low Dose Rate Investigation for Pulsed Reduced Dose Rate IMRT. Inter- national Journal of Medical Physics, Cli- nical Engineering and Radiation Oncology, 6, 139-149. https://doi.org/10.4236/ijmpcero.2017.62013