Jatinder Saini

Dosimetric evaluation of a commercial proton spot scanning Monte-Carlo dose algorithm: comparisons against measurements and simulations

RaySearch Americas Inc. (NY) has introduced a commercial Monte Carlo dose algorithm (RS-MC) for routine clinical use in proton spot scanning. In this report, we provide a validation of this algorithm against phantom measurements and simulations in the GATE software package. We also compared the performance of the RayStation analytical algorithm (RS-PBA) against the RS-MC algorithm. A beam model (G-MC) for a spot scanning gantry at our proton center was implemented in the GATE software package. The model was validated against measurements in a water phantom and was used for benchmarking the RS-MC. Validation of the RS-MC was performed in a water phantom by measuring depth doses and profiles for three spread-out Bragg peak (SOBP) beams with normal incidence, an SOBP with oblique incidence, and an SOBP with a range shifter and large air gap. The RS-MC was also validated against measurements and simulations in heterogeneous phantoms created by placing lung or bone slabs in a water phantom. Lateral dose profiles near the distal end of the beam were measured with a microDiamond detector and compared to the G-MC simulations, RS-MC and RS-PBA. Finally, the RS-MC and RS-PBA were validated against measured dose distributions in an Alderson-Rando (AR) phantom. Measurements were made using Gafchromic film in the AR phantom and compared to doses using the RS-PBA and RS-MC algorithms. For SOBP depth doses in a water phantom, all three algorithms matched the measurements to within  ±3% at all points and a range within 1 mm. The RS-PBA algorithm showed up to a 10% difference in dose at the entrance for the beam with a range shifter and  >30 cm air gap, while the RS-MC and G-MC were always within 3% of the measurement. For an oblique beam incident at 45°, the RS-PBA algorithm showed up to 6% local dose differences and broadening of distal fall-off by 5 mm. Both the RS-MC and G-MC accurately predicted the depth dose to within  ±3% and distal fall-off to within 2 mm. In an anthropomorphic phantom, the gamma index (dose tolerance  =  3%, distance-to-agreement  =  3 mm) was greater than 90% for six out of seven planes using the RS-MC, and three out seven for the RS-PBA. The RS-MC algorithm demonstrated improved dosimetric accuracy over the RS-PBA in the presence of homogenous, heterogeneous and anthropomorphic phantoms. The computation performance of the RS-MC was similar to the RS-PBA algorithm. For complex disease sites like breast, head and neck, and lung cancer, the RS-MC algorithm will provide significantly more accurate treatment planning.

Differential hepatic avoidance radiation therapy: Proof of concept in hepatocellular carcinoma patients

PURPOSE To evaluate the feasibility of a novel planning concept that differentially redistributes RT dose away from functional liver regions as defined by (99m)Tc-sulphur colloid (SC) uptake on patient SPECT/CT images. MATERIALS AND METHODS Ten HCC patients with different Child-Turcotte-Pugh scores (A5-B9) underwent SC SPECT/CT scans in treatment position prior to RT that were registered to planning CT scans. Proton pencil beam scanning (PBS) therapy plans were optimized to deliver 37.5-60.0Gy (RBE) over 5-15 fractions using single field uniform dose technique robust to range and setup uncertainty. Photon volumetrically modulated arc therapy (VMAT) plans were optimized to the same prescribed dose and minimum target coverage. For both treatment modalities, differential hepatic avoidance RT (DHART) plans were generated to decrease dose to functional liver volumes (FLV) defined by a range of thresholds relative to maximum SC uptake (43-90%) in the tumor-subtracted liver. Radiation dose was redistributed away from regions of increased SC uptake in each FLV by linearly scaling mean dose objectives during PBS or VMAT optimization. DHART planning feasibility was assessed by a significantly negative Spearmans rank correlation (RS) between dose difference and SC uptake. Patient, tumor, and treatment planning characteristics were tested for association to DHART planning feasibility using non-parametric Kruskal-Wallis ANOVA. RESULTS Compared to conventional plans, DHART plans achieved a 3% FLV dose reduction for every 10% SC uptake increase. DHART planning was feasible in the majority of patients with 60% of patients having RS<-0.5 (p<0.01, range -1.0 to 0.2) and was particularly effective in 30% of patients (RS<-0.9). Mean dose to FLV was reduced by up to 20% in these patients. Only fractionation regimen was associated with DHART planning feasibility: 15 fraction courses were more feasible than 5-6 fraction courses (RS<-0.93 vs. RS>-0.60, p<0.02). CONCLUSION Differential avoidance of functional liver regions defined on sulphur colloid SPECT/CT is achievable with either photon VMAT or proton PBS therapy. Further investigation with phantom studies and in a larger cohort of patients may validate the utility of DHART planning for HCC radiotherapy.

Functional lung avoidance and response‐adaptive escalation (FLARE) RT: Multimodality plan dosimetry of a precision radiation oncology strategy

Purpose Nonsmall cell lung cancer (NSCLC) patient radiation therapy (RT) is planned without consideration of spatial heterogeneity in lung function or tumor response. We assessed the dosimetric and clinical feasibility of functional lung avoidance and response‐adaptive escalation (FLARE) RT to reduce dose to [99mTc]MAA‐SPECT/CT perfused lung while redistributing an escalated boost dose within [18F]FDG‐PET/CT‐defined biological target volumes (BTV). Methods Eight stage IIB‐IIIB NSCLC patients underwent FDG‐PET/CT and MAA‐SPECT/CT treatment planning scans. Perfused lung objectives were derived from scatter/collimator/attenuation‐corrected MAA‐SPECT uptake relative to ITV‐subtracted lung to maintain < 20 Gy mean lung dose (MLD). Prescriptions included 60 Gy to the planning target volume (PTV) and concomitant boost of 74 Gy mean to biological target volumes (BTV = GTV + PET gradient segmentation) scaled to each BTV voxel by relative FDG‐PET SUV. Dose‐painting‐by‐numbers prescriptions were integrated into commercial treatment planning systems via uptake threshold discretization. Dose constraints for lung, heart, cord, and esophagus were defined. FLARE RT plans were optimized with volumetric modulated arc therapy (VMAT), proton pencil beam scanning (PBS) with 3%–3 mm robust optimization, and combination of PBS (avoidance) plus VMAT (escalation). The high boost dose region was evaluated within a standardized SUVpeak structure. FLARE RT plans were compared to reference VMAT plans. Linear regression between radiation dose to BTV and normalized FDG PET SUV at every voxel was conducted, from which Pearson linear correlation coefficients and regression slopes were extracted. Spearman rank correlation coefficients were estimated between radiation dose to lung and normalized SPECT uptake. Dosimetric differences between treatment modalities were evaluated by Friedman nonparametric paired test with multiple sampling correction. Results No unacceptable violations of PTV and normal tissue objectives were observed in 24 FLARE RT plans. Compared to reference VMAT plans, FLARE VMAT plans achieved a higher mean dose to BTV (73.7 Gy 98195. 61.3 Gy), higher mean dose to SUVpeak (89.7 Gy vs. 60.8 Gy), and lower mean dose to highly perfused lung (7.3 Gy vs. 14.9 Gy). These dosimetric gains came at the expense of higher mean heart dose (9.4 Gy vs. 5.8 Gy) and higher maximum cord dose (50.1 Gy vs. 44.6 Gy) relative to the reference VMAT plans. Between FLARE plans, FLARE VMAT achieved higher dose to the SUVpeak ROI than FLARE PBS (89.7 Gy vs. 79.2 Gy, P = 0.01), while FLARE PBS delivered lower dose to lung than FLARE VMAT (11.9 Gy vs. 15.6 Gy, P < 0.001). Voxelwise linear dose redistribution slope between BTV dose and FDG PET uptake was higher in magnitude for FLARE PBS + VMAT (0.36 Gy per %SUVmax) compared to FLARE VMAT (0.27 Gy per %SUVmax) or FLARE PBS alone (0.17 Gy per %SUVmax). Conclusions FLARE RT is clinically feasible with VMAT and PBS. A combination of PBS for functional lung avoidance and VMAT for FDG PET dose escalation balanced target and normal tissue objective tradeoffs. These results provide a technical platform for testing of FLARE RT safety and efficacy within a precision radiation oncology trial.

Clinical Commissioning of a Pencil Beam Scanning Treatment Planning System for Proton Therapy

Purpose In this report, we present the commissioning and validation results for a commercial proton pencil beam scanning RayStation treatment planning system. Materials and Methods The commissioning data requirements are (1) integrated depth dose curves, (2) spot profiles, (3) absolute dose/monitor unit calibration, and (4) virtual source position. An 8-cm parallel plate chamber was used to measure the integrated depth dose curves by scanning a beam composed of a single spot in a water phantom. The spot profiles were measured at 5 different planes using a 2-dimensional scintillation detector. The absolute dose/monitor unit calibration was based on dose measurements in single-layer fields of size 10 × 10 cm2. The virtual-source position was calculated from the change in spot spacing with the distance from the isocenter. The beam model validation consisted of a comparison against commissioning data as well as a new set of verification measurements. For end-to-end testing, a series of phantom plans were created. These plans were measured at 1 to 3 depths using a 2-dimensional ion chamber array and evaluated for gamma index using the 3% and 3 mm criteria. Results The maximum deviation for spot sigma measured versus calculated was -0.2 mm. The point-dose measurements for single-layer beams were within ± 3%, except for the largest field size (29 × 29 cm2) and the highest energy (226 MeV). The point doses in the spread-out Bragg peak plans showed a trend in which differences > 3% were seen for ranges > 30 cm, field sizes > 15 × 15 cm2, and depths > 25 cm. For end-to-end testing, 34 planes corresponding to 13 beams were analyzed for gamma index with a minimum pass rate of 92.8%. Conclusion The acceptable verification results and successful end-to-end testing ensured that all components of the treatment planning system were functional and the system was ready for clinical use.

Medical Physics residency programs in nonacademic facilities should affiliate themselves with a university-based program

Suggestions for topics suitable for these Point/Counterpoint debates should be addressed to Colin G. Orton, Professor Emeritus, Wayne State University, Detroit: ortonc@comcast.net. Persons participating in Point/Counterpoint discussions are selected for their knowledge and communicative skill. Their positions for or against a proposition may or may not reflect their personal opinions or the positions of their employers.

Biological and dosimetric characterisation of spatially fractionated proton minibeams

The biological effectiveness of proton beams varies with depth, spot size and lateral distance from the beam central axis. The aim of this work is to incorporate proton relative biological effectiveness (RBE) and equivalent uniform dose (EUD) considerations into comparisons of broad beam and highly modulated proton minibeams. A Monte Carlo model of a small animal proton beamline is presented. Dose and variable RBE is calculated on a per-voxel basis for a range of energies (30-109 MeV). For an open beam, the RBE values at the beam entrance ranged from 1.02-1.04, at the Bragg peak (BP) from 1.3 to 1.6, and at the distal end of the BP from 1.4 to 2.0. For a 50 MeV proton beam, a minibeam collimator designed to produce uniform dose at the depth of the BP peak, had minimal impact on the open beam RBE values at depth. RBE changes were observed near the surface when the collimator was placed flush with the irradiated object, due to a higher neutron contribution derived from proton interactions with the collimator. For proton minibeams, the relative mean RBE weighted entrance dose (RWD) was ~25% lower than the physical mean dose. A strong dependency of the EUD with fraction size was observed. For 20 Gy fractions, the EUD varied widely depending on the radiosensitivity of the cells. For radiosensitive cells, the difference was up to ~50% in mean dose and ~40% in mean RWD and the EUD trended towards the valley dose rather than the mean dose. For comparative studies of uniform dose with spatially fractionated proton minibeams, EUD derived from a per-voxel RWD distribution is recommended for biological assessments of reproductive cell survival and related endpoints.

Advanced proton beam dosimetry part I: review and performance evaluation of dose calculation algorithms

The accuracy of dose calculation is vital to the quality of care for patients undergoing proton beam therapy (PBT). Currently, the dose calculation algorithms available in commercial treatment planning systems (TPS) in PBT are classified into two classes: pencil beam (PB) and Monte-Carlo (MC) algorithms. PB algorithms are still regarded as the standard of practice in PBT, but they are analytical approximations whereas MC algorithms use random sampling of interaction cross-sections that represent the underlying physics to simulate individual particles trajectories. This article provides a brief review of PB and MC dose calculation algorithms employed in commercial treatment planning systems and their performance comparison in phantoms through simulations and measurements. Deficiencies of PB algorithms are first highlighted by a simplified simulation demonstrating the transport of a single sub-spot of proton beam that is incident at an oblique angle in a water phantom. Next, more typical cases of clinical beams in water phantom are presented and compared to measurements. The inability of PB to correctly predict the range and subsequently distal fall-off is emphasized. Through the presented examples, it is shown how dose errors as high as 30% can result with use of a PB algorithm. These dose errors can be minimized to clinically acceptable levels of less than 5%, if MC algorithm is employed in TPS. As a final illustration, comparison between PB and MC algorithm is made for a clinical beam that is use to deliver uniform dose to a target in a lung section of an anthropomorphic phantom. It is shown that MC algorithm is able to correctly predict the dose at all depths and matched with measurements. For PB algorithm, there is an increasing mismatch with the measured doses with increasing tissue heterogeneity. The findings of this article provide a foundation for the second article of this series to compare MC vs. PB based lung cancer treatment planning.

Intensity Modulated Proton Therapy with Advanced Planning Techniques in a Challenging Hepatocellular Carcinoma Patient

The use of radiation therapy has been increasing over recent years for the treatment of hepatocellular carcinoma (HCC). Proton beam therapy (PBT) has emerged as a promising treatment option for HCC patients due to its dosimetric advantages of sparing more normal liver tissue from radiation at low to moderate doses compared to photon-based treatments while still delivering high doses of radiation to tumors. The PBT therapy may be particularly beneficial in high-risk HCC cirrhotic patients with large, bulky tumors and/or vascular invasion complicated by surrounding perfusion abnormalities. We present a case of a 62-year-old male with an unresectable 13 cm diffusely infiltrative HCC tumor with main portal vein invasion and elevated alpha-feta protein (AFP) of 37,200 that was intolerant of standard sorafenib treatment. He was treated with hypofractionated PBT to 67.5 GyE in 15 fractions using a novel combination of simultaneously integrated boost intensity modulated proton therapy (SIB-IMPT), breath hold technique, and functional liver imaging with technetium-99m [99mTc] sulfur colloid single-photon emission computed tomography (SPECT/CT) to assist in the differentiation of tumor and normal liver. He had a complete radiographic and biochemical response by AFP normalization by seven months post-treatment without evidence of radiation hepatotoxicity.

Advanced proton beam dosimetry part II: Monte Carlo vs . pencil beam-based planning for lung cancer

Background Proton pencil beam (PB) dose calculation algorithms have limited accuracy within heterogeneous tissues of lung cancer patients, which may be addressed by modern commercial Monte Carlo (MC) algorithms. We investigated clinical pencil beam scanning (PBS) dose differences between PB and MC-based treatment planning for lung cancer patients. Methods With IRB approval, a comparative dosimetric analysis between RayStation MC and PB dose engines was performed on ten patient plans. PBS gantry plans were generated using single-field optimization technique to maintain target coverage under range and setup uncertainties. Dose differences between PB-optimized (PBopt), MC-recalculated (MCrecalc), and MC-optimized (MCopt) plans were recorded for the following region-of-interest metrics: clinical target volume (CTV) V95, CTV homogeneity index (HI), total lung V20, total lung VRX (relative lung volume receiving prescribed dose or higher), and global maximum dose. The impact of PB-based and MC-based planning on robustness to systematic perturbation of range (±3% density) and setup (±3 mm isotropic) was assessed. Pairwise differences in dose parameters were evaluated through non-parametric Friedman and Wilcoxon sign-rank testing. Results In this ten-patient sample, CTV V95 decreased significantly from 99-100% for PBopt to 77-94% for MCrecalc and recovered to 99-100% for MCopt (P<10-5). The median CTV HI (D95/D5) decreased from 0.98 for PBopt to 0.91 for MCrecalc and increased to 0.95 for MCopt (P<10-3). CTV D95 robustness to range and setup errors improved under MCopt (ΔD95 =-1%) compared to MCrecalc (ΔD95 =-6%, P=0.006). No changes in lung dosimetry were observed for large volumes receiving low to intermediate doses (e.g., V20), while differences between PB-based and MC-based planning were noted for small volumes receiving high doses (e.g., VRX). Global maximum patient dose increased from 106% for PBopt to 109% for MCrecalc and 112% for MCopt (P<10-3). Conclusions MC dosimetry revealed a reduction in target dose coverage under PB-based planning that was regained under MC-based planning along with improved plan robustness. MC-based optimization and dose calculation should be integrated into clinical planning workflows of lung cancer patients receiving actively scanned proton therapy.

SU-F-T-182: A Stochastic Approach to Daily QA Tolerances On Spot Properties for Proton Pencil Beam Scanning

PURPOSE Proton pencil beam scanning is used clinically across the United States. There are no current guidelines on tolerances for daily QA specific to pencil beam scanning, specifically related to the individual spot properties (spot width). Using a stochastic method to determine tolerances has the potential to optimize tolerances on individual spots and decrease the number of false positive failures in daily QA. Individual and global spot tolerances were evaluated. METHODS As part of daily QA for proton pencil beam scanning, a field of 16 spots (corresponding to 8 energies) is measured using an array of ion chambers (Matrixx, IBA). Each individual spot is fit to two Gaussian functions (x,y). The spot width (σ) in × and y are recorded (32 parameters). Results from the daily QA were retrospectively analyzed for 100 days of data. The deviations of the spot widths were histogrammed and fit to a Gaussian function. The stochastic spot tolerance was taken to be the mean ± 3σ. Using these results, tolerances were developed and tested against known deviations in spot width. RESULTS The individual spot tolerances derived with the stochastic method decreased in 30/32 instances. Using the previous tolerances (± 20% width), the daily QA would have detected 0/20 days of the deviation. Using a tolerance of any 6 spots failing the stochastic tolerance, 18/20 days of the deviation would have been detected. CONCLUSION Using a stochastic method we have been able to decrease daily tolerances on the spot widths for 30/32 spot widths measured. The stochastic tolerances can lead to detection of deviations that previously would have been picked up on monthly QA and missed by daily QA. This method could be easily extended for evaluation of other QA parameters in proton spot scanning.