Online adaptive radiotherapy: Assessment of planning technique and its impact on longitudinal plan quality robustness in pancreatic cancer.

BACKGROUND AND PURPOSE: Planning on a static dataset that reflects the simulation day anatomy is routine for SBRT. We hypothesize the quality of on-table adaptive plans is similar to the baseline plan when delivering stereotactic MR-guided adaptive radiotherapy (SMART) for pancreatic cancer (PCa). MATERIALS AND METHODS: Sixty-seven inoperable PCa patients were prescribed 50 Gy/5-fraction SMART. Baseline planning included: 3-5 mm gastrointestinal (GI) PRV, 50 Gy optimization target (PTVopt) based on GI PRV, conformality rings, and contracted GTV to guide the hotspot. For each adaptation, GI anatomy was re-contoured, followed by re-optimization. Plan quality was evaluated for target coverage (TC = PTVopt V100%/volume), PTV D90% and D80%, homogeneity index (HI = PTVopt D2%/D98%), prescription isodose/target volume (PITV), low-dose conformity (D2cm = maximum dose at 2 cm from PTVopt/Rx dose), and gradient index (R50%=50% Rx isodose volume/PTVopt volume).A novel global planning metric, termed the Pancreas Adaptive Radiotherapy Score (PARTS), was developed and implemented based on GI OAR sparing, PTV/GTV coverage, and conformality. Adaptive robustness (baseline to fraction 1) and stability (difference between two fractions with highest GI PRV variation) were quantified. RESULTS: OAR constraints were met on all baseline (n = 67) and adaptive (n = 318) plans. Coverage for baseline/adaptive plans was mean ± SD at 44.9 ± 5.8 Gy/44.3 ± 5.5 Gy (PTV D80%), 50.1 ± 4.2 Gy/49.1 ± 4.7 Gy (PTVopt D80%), and 80%±18%/74%±18% (TC), respectively. Mean homogeneity and conformality for baseline/adaptive plans were 0.87 ± 0.25/0.81 ± 0.30 (PITV), 3.81 ± 1.87/3.87 ± 2.0 (R50%), 1.53 ± 0.23/1.55 ± 0.23 (HI), and 58%±7%/59%±7% (D2cm), respectively. PARTS was found to be a sensitive metric due to its additive influence of geometry changes on PARTS' sub-metrics. There were no statistical differences (p > 0.05) for stability, except for PARTS (p = 0.04, median difference -0.6%). Statistical differences for robustness when significant were small for most metrics (<2.0% median). Median adaptive re-optimizations were 2. CONCLUSION: We describe a 5-fraction ablative SMART planning approach for PCa that is robust and stable during on-table adaption, due to gradients controlled by a GI PRV technique and the use of rings. These findings are noteworthy given that daily interfraction anatomic GI OAR differences are routine, thus necessitating on-table adaptation. This work supports feasibility towards utilizing a patient-independent, template on-table adaptive approach.

Dosimetric delivery validation of dynamically collimated pencil beam scanning proton therapy.

Objective. Pencil beam scanning (PBS) proton therapy target dose conformity can be improved with energy layer-specific collimation. One such collimator is the dynamic collimation system (DCS), which consists of four nickel trimmer blades that intercept the scanning beam as it approaches the lateral extent of the target. While the dosimetric benefits of the DCS have been demonstrated through computational treatment planning studies, there has yet to be experimental verification of these benefits for composite multi-energy layer fields. The objective of this work is to dosimetrically characterize and experimentally validate the delivery of dynamically collimated proton therapy with the DCS equipped to a clinical PBS system.Approach. Optimized single field, uniform dose treatment plans for 3 × 3 × 3 cm3target volumes were generated using Monte Carlo dose calculations with depths ranging from 5 to 15 cm, trimmer-to-surface distances ranging from 5 to 18.15 cm, with and without a 4 cm thick polyethylene range shifter. Treatment plans were then delivered to a water phantom using a prototype DCS and an IBA dedicated nozzle system and measured with a Zebra multilayer ionization chamber, a MatriXX PT ionization chamber array, and Gafchromic™ EBT3 film.Main results. For measurements made within the SOBPs, average 2D gamma pass rates exceeded 98.5% for the MatriXX PT and 96.5% for film at the 2%/2 mm criterion across all measured uncollimated and collimated plans, respectively. For verification of the penumbra width reduction with collimation, film agreed with Monte Carlo with differences within 0.3 mm on average compared to 0.9 mm for the MatriXX PT.Significance. We have experimentally verified the delivery of DCS-collimated fields using a clinical PBS system and commonly available dosimeters and have also identified potential weaknesses for dosimeters subject to steep dose gradients.

The dosimetric enhancement of GRID profiles using an external collimator in pencil beam scanning proton therapy.

PURPOSE: The radiobiological benefits afforded by spatially fractionated (GRID) radiation therapy pairs well with the dosimetric advantages of proton therapy. Inspired by the emergence of energy-layer specific collimators in pencil beam scanning (PBS), this work investigates how the spot spacing and collimation can be optimized to maximize the therapeutic gains of a GRID treatment while demonstrating the integration of a dynamic collimation system (DCS) within a commercial beamline to deliver GRID treatments and experimentally benchmark Monte Carlo calculation methods. METHODS: GRID profiles were experimentally benchmarked using a clinical DCS prototype that was mounted to the nozzle of the IBA-dedicated nozzle system. Integral depth dose (IDD) curves and lateral profiles were measured for uncollimated and GRID-collimated beamlets. A library of collimated GRID dose distributions were simulated by placing beamlets within a specified uniform grid and weighting the beamlets to achieve a volume-averaged tumor cell survival equivalent to an open field delivery. The healthy tissue sparing afforded by the GRID distribution was then estimated across a range of spot spacings and collimation widths, which were later optimized based on the radiosensitivity of the tumor cell line and the nominal spot size of the PBS system. This was accomplished by using validated models of the IBA universal and dedicated nozzles. RESULTS: Excellent agreement was observed between the measured and simulated profiles. The IDDs matched above 98.7% when analyzed using a 1%/1-mm gamma criterion with some minor deviation observed near the Bragg peak for higher beamlet energies. Lateral profile distributions predicted using Monte Carlo methods agreed well with the measured profiles; a gamma passing rate of 95% or higher was observed for all in-depth profiles examined using a 3%/2-mm criteria. Additional collimation was shown to improve PBS GRID treatments by sharpening the lateral penumbra of the beamlets but creates a trade-off between enhancing the valley-to-peak ratio of the GRID delivery and the dose-volume effect. The optimal collimation width and spot spacing changed as a function of the tumor cell radiosensitivity, dose, and spot size. In general, a spot spacing below 2.0 cm with a collimation less than 1.0 cm provided a superior dose distribution among the specific cases studied. CONCLUSIONS: The ability to customize a GRID dose distribution using different collimation sizes and spot spacings is a useful advantage, especially to maximize the overall therapeutic benefit. In this regard, the capabilities of the DCS, and perhaps alternative dynamic collimators, can be used to enhance GRID treatments. Physical dose models calculated using Monte Carlo methods were experimentally benchmarked in water and were found to accurately predict the respective dose distributions of uncollimated and DCS-collimated GRID profiles.

Systematic evaluation and plan quality assessment of the Leksell® gamma knife® lightning dose optimizer.

To compare stereotactic radiosurgery (SRS) plan quality metrics of manual forward planning (MFP) and Elekta Fast Inverse Planning™ (FIP)-based inversely optimized plans for patients treated with Gamma Knife®. Clinically treated, MFP SRS plans for 100 consecutive patients (115 lesions; 67 metastatic and 48 benign) were replanned with the FIP dose optimizer based on a convex linear programming formulation. Comparative plans were generated to match or exceed the following metrics in order of importance: Target Coverage (TC), Paddick Conformity Index (PCI), beam-on time (BOT), and Gradient Index (GI). Plan quality metrics and delivery parameters between MFP and FIP were compared for all lesions and stratified into subgroups for further analysis. Additionally, performance of FIP for multiple punctate (<4 mm) metastatic lesions on a subset of cases was investigated. A Wilcoxon signed-rank test for non-normal distributions was used to assess the statistical differences between the MFP and FIP treatment plans. Overall, 76% (87/115) of FIP plans showed a statistically significant improvement in plan quality compared to MFP plans. As compared to MFP, FIP plans demonstrated an increase in the median PCI by 1.1% (p<0.01), a decrease in GI by 3.7% (p< 0.01), and an increase in median number of shots by 74% (p< 0.01). TC and BOT were not statistically significantly different between MFP and FIP plans (p>0.05). FIP plans showed a statistically significant increase in use of 16 mm (p< 0.01) and blocked shots (p< 0.01), with a corresponding decrease in 4 mm shots (p< 0.01). Use of multiple shots per coordinate was significantly higher in FIP plans (p<0.01). The FIP optimizer failed to generate a clinically acceptable plan in 4/115 (3.5%) lesions despite optimization parameter changes. The mean optimization time for FIP plans was 5.0 min (Range: 1.0 - 10.0 min). In the setting of multiple punctate lesions, PCI for FIP was significantly improved (p<0.01) by changing the default low-dose/BOT penalty optimization setting from a default of 50/50 to 75-85/40. FIP offers a significant reduction in manual effort for SRS treatment planning while achieving comparable plan quality to an expert planner-substantially improving overall planning efficiency. FIP plans employ a non-intuitive increased use of blocked sectors and shot-in-shot technique to achieve high quality plans. Several FIP plans failed to achieve clinically acceptable treatments and warrant further investigation.

Development and validation of the Dynamic Collimation Monte Carlo simulation package for pencil beam scanning proton therapy.

PURPOSE: The aim of this work was to develop and experimentally validate a Dynamic Collimation Monte Carlo (DCMC) simulation package specifically designed for the simulation of collimators in pencil beam scanning proton therapy (PBS-PT). The DCMC package was developed using the TOPAS Monte Carlo platform and consists of a generalized PBS source model and collimator component extensions. METHODS: A divergent point-source model of the IBA dedicated nozzle (DN) at the Miami Cancer Institute (MCI) was created and validated against on-axis commissioning measurements taken at MCI. The beamline optics were mathematically incorporated into the source to model beamlet deflections in the X and Y directions at the respective magnet planes. Off-axis measurements taken at multiple planes in air were used to validate both the off-axis spot size and divergence of the source model. The DCS trimmers were modeled and incorporated as TOPAS geometry extensions that linearly translate and rotate about the bending magnets. To validate the collimator model, a series of integral depth dose (IDD) and lateral profile measurements were acquired at MCI and used to benchmark the DCMC performance for modeling both pristine and range shifted beamlets. The water equivalent thickness (WET) of the range shifter was determined by quantifying the shift in the depth of the 80% dose point distal to the Bragg peak between the range shifted and pristine uncollimated beams. RESULTS: A source model of the IBA DN system was successfully commissioned against on- and off-axis IDD and lateral profile measurements performed at MCI. The divergence of the source model was matched through an optimization of the source-to-axis distance and comparison against in-air spot profiles. The DCS model was then benchmarked against collimated IDD and in-air and in-phantom lateral profile measurements. Gamma analysis was used to evaluate the agreement between measured and simulated lateral profiles and IDDs with 1%/1 mm criteria and a 1% dose threshold. For the pristine collimated beams, the average 1%/1 mm gamma pass rates across all collimator configurations investigated were 99.8% for IDDs and 97.6% and 95.2% for in-air and in-phantom lateral profiles. All range shifted collimated IDDs passed at 100% while in-air and in-phantom lateral profiles had average pass rates of 99.1% and 99.8%, respectively. The measured and simulated WET of the polyethylene range shifter was determined to be 40.9 and 41.0 mm, respectively. CONCLUSIONS: We have developed a TOPAS-based Monte Carlo package for modeling collimators in PBS-PT. This package was then commissioned to model the IBA DN system and DCS located at MCI using both uncollimated and collimated measurements. Validation results demonstrate that the DCMC package can be used to accurately model other aspects of a DCS implementation via simulation.