Joshua B. Stoker

Exploratory Study of 4D versus 3D Robust Optimization in Intensity Modulated Proton Therapy for Lung Cancer.

PURPOSE The purpose of this study was to compare the impact of uncertainties and interplay on 3-dimensional (3D) and 4D robustly optimized intensity modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. METHODS AND MATERIALS IMPT plans were created for 11 nonrandomly selected non-small cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D computed tomography (CT) to irradiate clinical target volume (CTV). Regular fractionation (66 Gy [relative biological effectiveness; RBE] in 33 fractions) was considered. In 4D optimization, the CTV of individual phases received nonuniform doses to achieve a uniform cumulative dose. The root-mean-square dose-volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram (DVH) indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed rank test. RESULTS 4D robust optimization plans led to smaller AUC for CTV (14.26 vs 18.61, respectively; P=.001), better CTV coverage (Gy [RBE]) (D95% CTV: 60.6 vs 55.2, respectively; P=.001), and better CTV homogeneity (D5%-D95% CTV: 10.3 vs 17.7, respectively; P=.002) in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage (D95% CTV: 64.5 vs 63.8, respectively; P=.0068), comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. CONCLUSIONS Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic patient population is warranted to generalize the conclusions.

Intensity modulated proton therapy for craniospinal irradiation: Organ-at-risk exposure and a low-gradient junctioning technique

PURPOSE To compare field junction robustness and sparing of organs at risk (OARs) during craniospinal irradiation (CSI) using intensity modulated proton therapy (IMPT) to conventional passively scattered proton therapy (PSPT). METHODS AND MATERIALS Ten patients, 5 adult and 5 pediatric patients, previously treated with PSPT-based CSI were selected for comparison. Anterior oblique cranial fields, using a superior couch rotation, and posterior spinal fields were used for IMPT planning. To facilitate low-gradient field junctioning along the spine, the inverse-planning IMPT technique was divided into 3 stages. Dose indices describing target coverage and normal tissue dose, in silico error modeling, and film dosimetry were used to assess plan quality. RESULTS Field junction robustness along the spine was improved using the staged IMPT planning technique, reducing the worst case impact of a 4-mm setup error from 25% in PSPT to <5% of prescription dose. This was verified by film dosimetry for clinical delivery. Exclusive of thyroid dose in adult patients, IMPT plans demonstrated sparing of organs at risk as good or better than PSPT. Coverage of the cribriform plate for pediatric (V95% [percentage of volume of the target receiving at least 95% of the prescribed dose]; 87 ± 11 vs 92 ± 7) and adult (V95%; 94 ± 7 vs 100 ± 1) patients and the clinical target in pediatric (V95%; 98 ± 2 vs 100 ± 1) and adult (V95%; 100 ± 1 vs 100 ± 1) patients for PSPT and IMPT plans, respectively, were comparable or improved. For adult patients, IMPT target dose inhomogeneity was increased, as determined by heterogeneity index (HI) and inhomogeneity coefficient (IC). IMPT lowered maximum spinal cord dose, improved spinal dose homogeneity, and reduced exposure to other OARs. CONCLUSIONS IMPT has the potential to improve CSI plan quality and the homogeneity of intrafractional dose at match lines. The IMPT approach developed may also simplify treatments and reduce workload per patient relative to PSPT.

SU‐F‐BRD‐01: A Novel 4D Robust Optimization Mitigates Interplay Effect in Intensity‐Modulated Proton Therapy for Lung Cancer

Purpose: To compare the impact of interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans to treat lung cancer. Methods: Two IMPT plans were created for 11 non-small-cell-lung-cancer cases with 6–14 mm spots. 3D robust optimization generated plans on average CTs with the internal gross tumor volume density overridden to deliver 66 CGyE in 33 fractions to the internal target volume (ITV). 4D robust optimization generated plans on 4D CTs with the delivery of prescribed dose to the clinical target volume (CTV). In 4D optimization, the CTV of individual 4D CT phases received non-uniform doses to achieve a uniform cumulative dose. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Patient anatomy voxels were mapped from phase to phase via deformable image registration to score doses. Indices from dose-volume histograms were used to compare target coverage, dose homogeneity, and normal-tissue sparing. DVH indices were compared using Wilcoxon test. Results: Given the presence of interplay effect, 4D robust optimization produced IMPT plans with better target coverage and homogeneity, but slightly worse normal tissue sparing compared to 3D robust optimization (unit: Gy) [D95% ITV: 63.5 vs 62.0 (p=0.014), D5% - D95% ITV: 6.2 vs 7.3 (p=0.37), D1% spinal cord: 29.0 vs 29.5 (p=0.52), Dmean total lung: 14.8 vs 14.5 (p=0.12), D33% esophagus: 33.6 vs 33.1 (p=0.28)]. The improvement of target coverage (D95%,4D – D95%,3D) was related to the ratio RMA3/(TVx10−4), with RMA and TV being respiratory motion amplitude (RMA) and tumor volume (TV), respectively. Peak benefit was observed at ratios between 2 and 10. This corresponds to 125 – 625 cm3 TV with 0.5-cm RMA. Conclusion: 4D optimization produced more interplay-effect-resistant plans compared to 3D optimization. It is most effective when respiratory motion is modest compared to TV. NIH/NCI K25CA168984; Eagles Cancer Research Career Development; The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research; Mayo ASU Seed Grant; The Kemper Marley Foundation

SU‐E‐T‐693: Comparison of Discrete Spot Scanning and Passive Scattering Craniospinal Proton Irradiation

PURPOSE To compare plan robustness, dose variations at field junctions, and overall dose conformity to target between passive scattering and discrete spot scanning (DSS) proton craniospinal irradiation. METHODS A DSS treatment plan was generated for three craniospinal CT image sets. A forward planning approach was used to generate treatment plans for the cranium and lower spine, which exhibited dose tapering of about 10 Gy/cm towards the thoracic spine to facilitate the low-gradient field junctions. In-house software accomplished optimization of discrete spot weights for the thoracic-level field, which was then imported into the Varian Eclipse clinical treatment planning system for dose calculation. Planning was guided using clinical targets defined for craniospinal irradiation with passively scattered proton beams. Robustness analysis was performed by varying the position of each beam isocenter +/-3 mm along each cardinal axis, simulating setup errors, as well as adjusting the CT number to relative stopping power curve to mimic +/-3.5% range variation, and then analyzing the resulting dose distribution. Dose profiles along the craniospinal axis were used to evaluate intrafraction dose variation at field junctions. Dose volume histograms (DVH) were generated for each robustness element, and then combined to create composite DVH illustrating a range of possible delivered dose. RESULTS Results of robustness analysis indicate that field isocenter shifts along the craniospinal axis can Result in dose intrafraction variations at the junction in excess of 25% for passive scattering proton plans. This value is markedly reduced for the same shifts applied to DSS plans using a tapered-dose field matching technique. CONCLUSION This work demonstrates the potential for improved robustness of proton craniospinal irradiations using a DSS delivery method, as well as significant decreases in clinic expenses. The use of apertures to define the sagittal plane field edge for DSS delivery improves the dose to target.

Automation of Routine Elements for Spot-Scanning Proton Patient-Specific Quality Assurance

PURPOSE At our institution, all proton patient plans undergo patient-specific quality assurance (PSQA) prior to treatment delivery. For intensity-modulated proton beam therapy, quality assurance is complex and time consuming, and it may involve multiple measurements per field. We reviewed our PSQA workflow and identified the steps that could be automated and developed solutions to improve efficiency. METHODS We used the treatment planning systems (TPS) capability to support C# scripts to develop an Eclipse scripting application programming interface (ESAPI) script and automate the preparation of the verification phantom plan for measurements. A local area network (LAN) connection between our measurement equipment and shared database was established to facilitate equipment control, measurement data transfer, and storage. To improve the analysis of the measurement data, a Python script was developed to automatically perform a 2D-3D γ-index analysis comparing measurements in the plane of a two-dimensional detector array with TPS predictions in a water phantom for each acquired measurement. RESULTS Device connection via LAN granted immediate access to the plan and measurement information for downstream analysis using an online software suite. Automated scripts applied to verification plans reduced time from preparation steps by at least 50%; time reduction from automating γ-index analysis was even more pronounced, dropping by a factor of 10. On average, we observed an overall time savings of 55% in completion of the PSQA per patient plan. CONCLUSIONS The automation of the routine tasks in the PSQA workflow significantly reduced the time required per patient, reduced user fatigue, and frees up system users from routine and repetitive workflow steps allowing increased focus on evaluating key quality metrics.

Multiple energy extraction reduces beam delivery time for a synchrotron-based proton spot-scanning system

Purpose Multiple energy extraction (MEE) is a technology that was recently introduced by Hitachi for its spot-scanning proton treatment system, which allows multiple energies to be delivered in a single synchrotron spill. The purpose of this paper is to investigate how much beam delivery time (BDT) can be reduced with MEE compared with single energy extraction (SEE), in which one energy is delivered per spill. Methods and Materials A recently developed model based on BDT measurements of our synchrotrons delivery performance was used to compute BDT. The total BDT for 2694 beam deliveries in a cohort of 79 patients treated at our institution was computed in both SEE and 9 MEE configurations to determine BDT reduction. The cohort BDT reduction was also calculated for hypothetical accelerators with increased deliverable charge and compared with the results of our current delivery system. Results A vendor-provided MEE configuration with 4 energy layers per spill reduced the total BDT on average by 35% (41 seconds) compared with SEE, with up to 65% BDT reduction for individual fields. Adding an MEE layer reduced the total BDT by <1% of SEE BDT. However, improving charge recapture efficiency increased BDT savings by up to 42% of SEE BDT. Conclusions The MEE delivery technique reduced the total BDT by 35%. Increasing the charge per spill and charge recapture efficiency is necessary to further reduce BDT and thereby take full advantage of our MEE systems potential to improve treatment delivery efficiency and operational throughput.

Use of a radial projection to reduce the statistical uncertainty of spot lateral profiles generated by Monte Carlo simulation

Abstract Monte Carlo (MC) simulation has been used to generate commissioning data for the beam modeling of treatment planning system (TPS). We have developed a method called radial projection (RP) for postprocessing of MC‐simulation‐generated data. We used the RP method to reduce the statistical uncertainty of the lateral profile of proton pencil beams with axial symmetry. The RP method takes advantage of the axial symmetry of dose distribution to use the mean value of multiple independent scores as the representative score. Using the mean as the representative value rather than any individual score results in substantial reduction in statistical uncertainty. Herein, we present the concept and step‐by‐step implementation of the RP method, as well as show the advantage of the RP method over conventional measurement methods for generating lateral profile. Lateral profiles generated by both methods were compared to demonstrate the uncertainty reduction qualitatively, and standard error comparison was performed to demonstrate the reduction quantitatively. The comparisons showed that statistical uncertainty was reduced substantially by the RP method. Using the RP method to postprocess MC data, the corresponding MC simulation time was reduced by a factor of 10 without quality reduction in the generated result from the MC data. We concluded that the RP method is an effective technique to increase MC simulation efficiency for generating lateral profiles for axially symmetric pencil beams.

Spot scanning proton therapy plan assessment: design and development of a dose verification application for use in routine clinical practice

The use of radiation therapy for the treatment of cancer has been carried out clinically since the late 1800’s. Early on however, it was discovered that a radiation dose sufficient to destroy cancer cells can also cause severe injury to surrounding healthy tissue. Radiation oncologists continually strive to find the perfect balance between a dose high enough to destroy the cancer and one that avoids damage to healthy organs. Spot scanning or “pencil beam” proton radiotherapy offers another option to improve on this. Unlike traditional photon therapy, proton beams stop in the target tissue, thus better sparing all organs beyond the targeted tumor. In addition, the beams are far narrower and thus can be more precisely “painted” onto the tumor, avoiding exposure to surrounding healthy tissue. To safely treat patients with proton beam radiotherapy, dose verification should be carried out for each plan prior to treatment. Proton dose verification systems are not currently commercially available so the Department of Radiation Oncology at the Mayo Clinic developed its own, called DOSeCHECK, which offers two distinct dose simulation methods: GPU-based Monte Carlo and CPU-based analytical. The three major components of the system include the web-based user interface, the Linux-based dose verification simulation engines, and the supporting services and components. The architecture integrates multiple applications, libraries, platforms, programming languages, and communication protocols and was successfully deployed in time for Mayo Clinic’s first proton beam therapy patient. Having a simple, efficient application for dose verification greatly reduces staff workload and provides additional quality assurance, ultimately improving patient safety.

SU‐E‐T‐400: Evaluation of Shielding and Activation at Two Pencil Beam Scanning Proton Facilities

Purpose: To verify acceptably low dose levels around two newly constructed identical pencil beam scanning proton therapy facilities and to evaluate accuracy of pre-construction shielding calculations. Methods: Dose measurements were taken at select points of interest using a WENDI-2 style wide-energy neutron detector. Measurements were compared to pre-construction shielding calculations. Radiation badges with neutron dose measurement capabilities were worn by personnel and also placed at points throughout the facilities. Seven neutron and gamma detectors were permanently installed throughout the facility, continuously logging data. Potential activation hazards have also been investigated. Dose rates near water tanks immediately after prolonged irradiation have been measured. Equipment inside the treatment room and accelerator vault has been surveyed and/or wipe tested. Air filters from air handling units, sticky mats placed outside of the accelerator vault, and water samples from the magnet cooling water loops have also been tested. Results: All radiation badges have been returned with readings below the reporting minimum. Measurements of mats, air filters, cooling water, wipe tests and surveys of equipment that has not been placed in the beam have all come back at background levels. All survey measurements show the analytical shielding calculations to be conservative by at least a factor of 2. No anomalous events have been identified by the building radiation monitoring system. Measurements of dose rates close to scanning water tanks have shown dose rates of approximately 10 mrem/hr with a half-life less than 5 minutes. Measurements around the accelerator show some areas with dose rates slightly higher than 10 mrem/hr. Conclusion: The shielding design is shown to be adequate. Measured dose rates are below those predicted by shielding calculations. Activation hazards are minimal except in certain very well defined areas within the accelerator vault and for objects placed directly in the path of the beam.

SU-E-T-618: Plan Robustness Study of Volumetric-Modulated Arc Therapy Vs. Intensity-Modulated Radiation Therapy for Head and Neck Cancer

Purpose: Lack of plan robustness may contribute to local failure in volumetric-modulated arc therapy (VMAT) to treat head and neck (H&N) cancer. Thus we compared plan robustness of VMAT with intensity-modulated radiation therapy (IMRT). Methods: VMAT and IMRT plans were created for 9 HN (2) dose-volume histograms (DVHs) band (DVHB); and (3) root-mean-square-dose deviation (RMSD) volume histogram (DDVH). DDVH represents the relative volume (y) on the vertical axis and the RMSD (x) on the horizontal axis. Similar to DVH, this means that y% of the volume of the indicated structure has the RMSD at least x Gy[RBE].The width from the first two methods at different target DVH indices (such as D95 and D5) and the area under the DDVH curves (AUC) for the target were used to indicate plan robustness. In these robustness quantification tools, the smaller the value, the more robust the plan is. Plan robustness evaluation metrics were compared using Wilcoxon test. Results: DVHB showed the width at D95 from IMRT to be larger than from VMAT (unit Gy) [1.59 vs 1.18 (p=0.49)], while the width at D5 from IMRT was found to be slightly larger than from VMAT [0.59 vs 0.54 (p=0.84)]. WCA showed similar results [D95: 3.28 vs 3.00 (p=0.56); D5: 1.68 vs 1.95 (p=0.23)]. DDVH showed the AUC from IMRT to be slightly smaller than from VMAT [1.13 vs 1.15 (p=0.43)]. Conclusion: VMAT plan robustness is comparable to IMRT plan robustness. The plan robustness conclusions from WCA and DVHB are DVH parameter dependent. On the other hand DDVH captures the overall effect of uncertainties on the dose to a volume of interest. NIH/NCI K25CA168984; Eagles Cancer Research Career Development; The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research Mayo ASU Seed Grant; The Kemper Marley Foundation