Generation and evaluation of anatomy-preserving virtual CT for online adaptive proton therapy.

BACKGROUND: Daily CTs generated by CBCT correction are required for daily replanning in online-adaptive proton therapy (APT) to effectively deal with inter-fractional changes. Out of the currently available methods, the suitability of a daily CT generation method for proton dose calculation also depends on the anatomical site. PURPOSE: We propose an anatomy-preserving virtual CT (APvCT) method as a hybrid method of CBCT correction, which is especially suitable for large anatomy deformations. The accuracy of the hybrid method was assessed by comparison with the corrected CBCT (cCBCT) and virtual CT (vCT) methods in the context of online APT. METHODS: Seventy-one daily CBCTs of four prostate cancer patients treated with intensity modulated proton therapy (IMPT) were converted to daily CTs using cCBCT, vCT, and the newly proposed APvCT method. In APvCT, planning CT (pCT) were mapped to CBCT geometry using deformable image registration with boundary conditions on controlling regions of interest (ROIs) created with deep learning segmentation on cCBCT. The relative frequency distribution (RFD) of HU, mass density and stopping power ratio (SPR) values were assessed and compared with the pCT. The ROIs in the APvCT and vCT were compared with cCBCT in terms of Dice similarity coefficient (DSC) and mean distance-to-agreement (mDTA). For each patient, a robustly optimized IMPT plan was created on the pCT and subsequent daily adaptive plans on daily CTs. For dose distribution comparison on the same anatomy, the daily adaptive plans on cCBCT and vCT were recalculated on the corresponding APvCT. The dose distributions were compared in terms of isodose volumes and 3D global gamma-index passing rate (GPR) at γ(2%, 2 mm) criterion. RESULTS: For all patients, no noticeable difference in RFDs was observed amongst APvCT, vCT, and pCT except in cCBCT, which showed a noticeable difference. The minimum DSC value was 0.96 and 0.39 for contours in APvCT and vCT respectively. The average value of mDTA for APvCT was 0.01 cm for clinical target volume and ≤0.01 cm for organs at risk, which increased to 0.18 cm and ≤0.52 cm for vCT. The mean GPR value was 90.9%, 64.5%, and 67.0% for APvCT versus cCBCT, vCT versus cCBCT, and APvCT versus vCT, respectively. When recalculated on APvCT, the adaptive cCBCT and vCT plans resulted in mean GPRs of 89.5 ± 5.1% and 65.9 ± 19.1%, respectively. The mean DSC values for 80.0%, 90.0%, 95.0%, 98.0%, and 100.0% isodose volumes were 0.97, 0.97, 0.97, 0.95, and 0.91 for recalculated cCBCT plans, and 0.89, 0.88, 0.87, 0.85, and 0.81 for recalculated vCT plans. Hausdorff distance for the 100.0% isodose volume in some cases of recalculated cCBCT plans on APvCT exceeded 1.00 cm. CONCLUSIONS: APvCT contours showed good agreement with reference contours of cCBCT which indicates anatomy preservation in APvCT. A vCT with erroneous anatomy can result in an incorrect adaptive plan. Further, slightly lower values of GPR between the APvCT and cCBCT-based adaptive plans can be explained by the difference in the cCBCT's SPR RFD from the pCT.

Benchmarking a New Circular Cone-based Radiosurgery System against Clinically Tested Radiosurgery System on the same Novel Digital Linear Accelerator Platform.

Objective: To examine the dosimetric characteristics of circular cones, the accuracy of dose modeling and overall treatment delivery of two radiosurgery systems integrated on a linear accelerator (Linac). Materials and Methods: The dosimetric characteristics of circular cones (4-17.5 mm) from Varian (VC) and BrainLAB (BLC) were measured for 6 MV flattening filter free beam from Edge linac using stereotactic field diode and 0.65 cc ionization chamber following established protocols. The Eclipse and iPlan modeled dose distribution for VCs and BLCs were validated with EBT3-film measurement. End-to-end tests were performed using stereotactic phantom having PTW 60008 diode connected to a Dose-1 electrometer. Results: The depth at dose maximum, TRP2010 and dose at 10cm depth of the same size VC and BLC agree within ± 0.7 mm, ± 0.71% and ± 0.81% respectively. Full width at half maximum (FWHM) of any cone beyond 15 mm depth increases at 1% of nominal cone size per 10 mm depth. The penumbra of 4mm and 17.5mm VC at 15 mm depth was 1.1 mm and 1.50 mm. At 300 mm depth, penumbra increased by around 0.4 mm for 4 mm cone and up to 1 mm for cone size ≥12.5 mm. The VCs penumbra values were within ±1mm of the corresponding BLCs. Scatter factors for VCs varies from 0.609 to 0.841 and were within ± 1.0% of corresponding values of BLCs. Agreement between the Eclipse and iPlan computed dose fluence and the EBT3-film measured dose fluence was >98% (γ: 1%@1 mm), and the absolute dose difference was ≤ 2.2%, except for the 4 mm cone in which it was >96% and ≤4.83%. Target localization using cone-beam computed tomography was accurate within ± 0.8 mm and ± 0.3° in translation and rotation. The end-to-end dose delivery accuracy for both radiosurgery systems was within ± 3.62%. Conclusion: The dosimetric characteristics of Varian and BLC cones of same diameter was comparable. Both Eclipse and iPlan cone planning system modeled dose fluences agree well with the EBT3 film measurement. The end-to-end tests revealed an excellent target localization accuracy of Edge linac with satisfactory and comparable absolute dose agreement between Varian and BLC radiosurgery systems and hence these can be interchanged on edge linac.

IMPT of head and neck cancer: unsupervised machine learning treatment planning strategy for reducing radiation dermatitis.

Radiation dermatitis is a major concern in intensity modulated proton therapy (IMPT) for head and neck cancer (HNC) despite its demonstrated superiority over contemporary photon radiotherapy. In this study, dose surface histogram data extracted from forty-four patients of HNC treated with IMPT was used to predict the normal tissue complication probability (NTCP) of skin. Grades of NTCP-skin were clustered using the K-means clustering unsupervised machine learning (ML) algorithm. A new skin-sparing IMPT (IMPT-SS) planning strategy was developed with three major changes and prospectively implemented in twenty HNC patients. Across skin surfaces exposed from 10 (S10) to 70 (S70) GyRBE, the skin's NTCP demonstrated the strongest associations with S50 and S40 GyRBE (0.95 and 0.94). The increase in the NTCP of skin per unit GyRBE is 0.568 for skin exposed to 50 GyRBE as compared to 0.418 for 40 GyRBE. Three distinct clusters were formed, with 41% of patients in G1, 32% in G2, and 27% in G3. The average (± SD) generalised equivalent uniform dose for G1, G2, and G3 clusters was 26.54 ± 6.75, 38.73 ± 1.80, and 45.67 ± 2.20 GyRBE. The corresponding NTCP (%) were 4.97 ± 5.12, 48.12 ± 12.72 and 87.28 ± 7.73 respectively. In comparison to IMPT, new IMPT-SS plans significantly (P < 0.01) reduced SX GyRBE, gEUD, and associated NTCP-skin while maintaining identical dose volume indices for target and other organs at risk. The mean NTCP-skin value for IMPT-SS was 34% lower than that of IMPT. The dose to skin in patients treated prospectively for HNC was reduced by including gEUD for an acceptable radiation dermatitis determined from the local patient population using an unsupervised MLA in the spot map optimization of a new IMPT planning technique. However, the clinical finding of acute skin toxicity must also be related to the observed reduction in skin dose.

Dosimetric impact of random spot positioning errors in intensity modulated proton therapy plans of small and large volume tumors.

OBJECTIVE: To study dosimetric impact of random spot positioning errors on the clinical pencil beam scanning proton therapy plans. METHODS AND MATERIALS: IMPT plans of 10 patients who underwent proton therapy for tumors in brain or pelvic regions representing small and large volumes, respectively, were included in the study. Spot positioning errors of 1 mm, -1 mm or ±1 mm were introduced in these clinical plans by modifying the geometrical co-ordinates of proton spots using a script in the MATLAB programming environment. Positioning errors were simulated to certain numbers of (20%, 40%, 60%, 80%) randomly chosen spots in each layer of these treatment plans. Treatment plans with simulated errors were then imported back to the Raystation (Version 7) treatment planning system and the resultant dose distribution was calculated using Monte-Carlo dose calculation algorithm.Dosimetric plan evaluation parameters for target and critical organs of nominal treatment plans delivered for clinical treatments were compared with that of positioning error simulated treatment plans. For targets, D95% and D2% were used for the analysis. Dose received by optic nerve, chiasm, brainstem, rectum, sigmoid, and bowel were analyzed using relevant plan evaluation parameters depending on the critical structure. In case of intracranial lesions, the dose received by 0.03 cm3 volume (D0.03 cm3) was analyzed for optic nerve, chiasm and brainstem. In rectum, the volume of it receiving a dose of 65 Gy(RBE) (V65) and 40 Gy(RBE) (V40) were compared between the nominal and error introduced plans. Similarly, V65 and V63 were analyzed for Sigmoid and V50 and V15 were analyzed for bowel. RESULTS: The maximum dose variation in PTV D95% (1.88 %) was observed in a brain plan in which the target volume was the smallest (2.7 cm3) among all 10 plans included in the study. This variation in D95% drops down to 0.3% for a sacral chordoma plan in which the PTV volume is significantly higher at 672 cm3. The maximum difference in OARs in terms of absolute dose (D0.03 cm3) was found in left optic nerve (9.81%) and the minimum difference was observed in brainstem (2.48%). Overall, the magnitude of dose errors in chordoma plans were less significant in comparison to brain plans. CONCLUSION: The dosimetric impact of different error scenarios in spot positioning becomes more prominent for treatment plans involving smaller target volume compared to plans involving larger target volumes. ADVANCES IN KNOWLEDGE: Provides information on the dosimetric impact of various possible spot positioning errors and its dependence on the tumor volume in intensity modulated proton therapy.

A novel hybrid 3D dose reconstruction approach for pre-treatment verification of intensity modulated proton therapy plans.

AIM: A novel hybrid three-dimensional (3D) dose reconstruction method, based on planar dose measured at a single shallower depth, was developed for use as patient-specific quality assurance (PSQA) of intensity modulated proton therapy (IMPT) plans. The accuracy, robustness and sensitivity of the presented method were validated for multiple IMPT plans of varying complexities. METHODS AND MATERIALS: An in-house MATLAB program was developed to reconstruct 3D dose distribution from the planar dose (GyRBE) measured at 3 g cm-2 depth in water or solid phantom using a MatriXX PT ion chamber array. The presented method was validated extensively for 11 single-field optimization (SFO) and multi-field optimization (MFO) plans on Proteus Plus. A total of 47 reconstructed planar doses at different depths were compared against the corresponding RayStation treatment planning system (TPS) and MatriXX PT measurement using a gamma passing rate (γ%) evaluated for 3%/3 mm. The robustness of the reconstruction method with respect to depth, energy layers, field dimensions and complexities in the spot intensity map (SIM) were analysed and compared against the standard PSQA. The sensitivity of the reconstruction method was tested for plans with intentional errors. RESULTS: The presented reconstruction method showed excellent agreement (mean γ% > 98%) and robustness with both TPS-calculated and measured dose planes at all depths (2.97-30 g cm-2), energy layers (82.1-225.5 MeV), field dimensions, target volume (17.7-1000 cm3) and SIMs from both SFO and MFO plans. In comparison to the overall mean ± SD γ% from standard PSQA, the reconstruction method showed reductions in mean γ% within 1% for both standard cubes and clinical plans. The reconstruction method was sensitive enough to detect intentional spot positional errors in a selected energy layer of a plan. CONCLUSION: The presented hybrid reconstruction method is sufficiently accurate, robust and sensitive to estimate planar dose at any user-defined depth. It simplifies the measurement setup and eliminates multiple depth measurements.

Leaf open time sinogram (LOTS): a novel approach for patient specific quality assurance of total marrow irradiation.

There is no ideal detector-phantom combination to perform patient specific quality assurance (PSQA) for Total Marrow (TMI) and Lymphoid (TMLI) Irradiation plan. In this study, 3D dose reconstruction using mega voltage computed tomography detectors measured Leaf Open Time Sinogram (LOTS) was investigated for PSQA of TMI/TMLI patients in helical tomotherapy. The feasibility of this method was first validated for ten non-TMI/TMLI patients, by comparing reconstructed dose with (a) ion-chamber (IC) and helical detector array (ArcCheck) measurement and (b) planned dose distribution using 3Dγ analysis for 3%@3mm and dose to 98% (D98%) and 2% (D2%) of PTVs. Same comparison was extended for ten treatment plans from five TMI/TMLI patients. In all non-TMI/TMLI patients, reconstructed absolute dose was within ± 1.80% of planned and IC measurement. The planned dose distribution agreed with reconstructed and ArcCheck measured dose with mean (SD) 3Dγ of 98.70% (1.57%) and 2Dγ of 99.48% (0.81%). The deviation in D98% and D2% were within 1.71% and 4.10% respectively. In all 25 measurement locations from TMI/TMLI patients, planned and IC measured absolute dose agreed within ± 1.20%. Although sectorial fluence verification using ArcCHECK measurement for PTVs chest from the five upper body TMI/TMLI plans showed mean ± SD 2Dγ of 97.82% ± 1.27%, the reconstruction method resulted poor mean (SD) 3Dγ of 92.00% (± 5.83%), 64.80% (± 28.28%), 69.20% (± 30.46%), 60.80% (± 19.37%) and 73.2% (± 20.36%) for PTVs brain, chest, torso, limb and upper body respectively. The corresponding deviation in median D98% and D2% of all PTVs were < 3.80% and 9.50%. Re-optimization of all upper body TMI/TMLI plans with new pitch and modulation factor of 0.3 and 3 leads significant improvement with 3Dγ of 100% for all PTVs and median D98% and D2% < 1.6%. LOTS based PSQA for TMI/TMLI is accurate, robust and efficient. A field width, pitch and modulation factor of 5 cm, 0.3 and 3 for upper body TMI/TMLI plan is suggested for better dosimetric outcome and PSQA results.

Ambient neutron and photon dose equivalent H*(10) around a pencil beam scanning proton therapy facility.

OBJECTIVES: To measure leakage ambient dose equivalent H*(10) from stray secondary neutron and photon radiation around proton therapy (PT) facility and evaluate adequacy of shielding design. METHODS AND MATERIALS: H*(10) measurement were carried out at 149 locations around cyclotron vault (CV), beam transport system (BTS) and first treatment room (GTR3) of a multiroom PT facility using WENDI-II and SmartIon survey meter. Measurement were performed under extreme case scenarios wherein maximum secondary neutrons and photons were produced around CV, BTS and GTR3 by stopping 230MeV proton of 300nA on beam degrader, end of BTS and isocenter of GTR3. Weekly time average dose rate (TADR) were calculated from H*(10) value measured at selective hot spots by irradiating actual treatment plans of mix clinical sites. RESULTS: The maximum total H*(10) were within 2 µSv/hr around CV, 5 µSv/hr around outer wall of BTS which increases up to 62 µSv/hr at the end of inside BTS corridor. Maximum H*(10) of 20.8 µSv/hr in treatment control console (P125), 23.4 µSv/hr behind the common wall between GTR3 and GTR2 (P132) and 25.7 µSv/hr above isocenter (P99) were observed around GTR3. Reduction of beam current from 6 to 3 nA and 1 nA at nozzle exit lead to decrease in total H*(10) at P125 from 20.8 to 11.35 and 4.62 µSv/hr. In comparison to extreme case scenario, H*(10) value at P125, P132 and P99 from clinically relevant irradiation parameters were reduce by a factor ranging from 8.6 for high range cube to 46.4 for brain clinical plan. The maximum weekly TADR per fraction was highest for large volume, sacral chordoma patient at 8.5 µSv/hr compare to 0.3 µSv/hr for brain patient. The calculated weekly TADR for 30 mix clinical cases and 15 fractions of 1 L cube resulted total weekly TADR of 83-84 µSv/hr at P125, P132 and P99. The maximum annual dose level at these hot spots were estimated at 4.37 mSv/Yr. CONCLUSION: We have carried out an extensive measurement of H*(10) under different conditions. The shielding thickness of our PT facility is adequate to limit the dose to occupational worker and general public within the permissible stipulated limit. The data reported here can bridge the knowledge gap in ambient dose around PT facility and can also be used as a reference for any new and existing proton facility for intercomparison and validation. ADVANCES IN KNOWLEDGE: First extensive investigation of neutron and photon H*(10) around PT facility and can bridge the knowledge gap on ambient dose.

Physical and dosimetric characteristic of high-definition multileaf collimator (HDMLC) for SRS and IMRT.

Physical and dosimetric characteristics of HDMLC were studied for SRS6, 6, and 10 MV X-rays from Novalis Tx. This in-built tertiary collimator consists of 60 pairs (32 × 0.25 cm; 26 × 0.5 cm and 2 × 0.7 cm) of leaves. Properties of HDMLC studied included alignment, readout and radiation field congruence, radiation penumbra, accuracy and reproducibility of leaf position and gap width, static and dynamic leaf shift, tongue-and-groove effect, leaf transmission and leakage, leaf travel speed, and delivery of dynamic conformal arc and IMRT. All tests were performed using a calibrated ionization chamber, film dosimetry and DynaLog file analysis. Alignment of leaves with isocenter plane was better than 0.03 cm at all gantry and collimator positions. The congruence of HDMLC readout and radiation field agreed to within ± 0.03 cm for filed sizes ranging from 1 × 1 to 20 × 20 cm2. Mean 80% to 20% penumbra width parallel (perpendicular) to leaf motion was 0.24 ± 0.05 (0.21 ± 0.02) cm, 0.37 ± 0.12 (0.29 ± 0.07) cm, and 0.51 ± 0.13 (0.43± 0.07) cm for SRS6, 6, and 10 MV X-rays, respectively. Circular field penumbra was comparable to corresponding square field. Average penumbra of 1 × 20 cm2 field was effectively constant over off-axis positions of up to 12 cm with mean value of 0.16 (± 0.01) cm at 1.5 cm depth and 0.38 (± 0.04) cm at 10 cm depth. Minimum and maximum effective penumbra along the straight diagonal edge of irregular fields increased from 0.3 and 0.32 cm at 70° steep angle to 0.35 and 0.56 cm at 20° steep angle. Modified Picket Fence test showed average FWHM of 0.18 cm and peak-to-peak distance of 1.99 cm for 0.1 cm band and 2 cm interband separation. Dynamic multileaf collimation (DMLC) output factor remained within ± 1% for 6 MV and ± 0.5% for 10 MV X-rays at all gantry positions, and was reproducible within ± 0.5% over a period of 14 months. The static leaf shift was 0.03 cm for all energies, while dynamic leaf shift was 0.044 cm for 10 MV and 0.039 cm for both SRS6 and 6 MV X-rays. The dose depression and corresponding tongue-and-groove size were 24% and 0.17 cm for 6 MV and 19% and 0.20 cm for 10 MV X-rays. Average transmission through HDMLC was 1.09%, 1.14% and 1.34% for SRS6, 6 and 10 MV X-rays. Analysis of DynaLog files for leaf speed test in arc dynamic mode, delivery test of dynamic conformal arc, and step-and-shoot and sliding window IMRT showed at least 95% or more of the error counts had misplacements < 0.2 cm, with maximum root mean square (RMS) error value calculated at 0.13cm. Accurate and reproducible leaf position and gap width, and less leakage and small consistent penumbra over the fields demonstrate HDMLC suitable for high-dose resolution SRS and IMRT.

Portal dosimetry for pretreatment verification of IMRT plan: a comparison with 2D ion chamber array.

Portal dosimetry (PD) was performed for 181 fields from 14 IMRT plans of various clinical sites at gantry zero and source-to-detector distance (SDD) of 100 cm. PD was realized using aSi1000 electronic portal imaging device (EPID) and portal dose prediction (PDP) algorithm implemented in Eclipse treatment planning system (TPS). Agreement of PDP predicted and EPID measured photon fluence/dose distribution were evaluated using gamma (γ) index set at 3% at 3 mm distance to point agreement (DTA). Three gamma scaling parameters, maximum γ (γ(max)), average γ (γ(avg)) and percentage of points with γ ≤ 1 (γ% ≤ 1) were estimated for each field. An independent measurement was carried out using MatriXX 2D ion chamber array with detector plane at 100 cm and γ(max), γ(avg) and γ% ≤ 1 were estimated using OmniPro IMRT analyzing software. Effect of extended SDD and gantry rotation on portal dosimetry outcome was also investigated for another 45 IMRT fields. PDP predicted and EPID measured photon fluence agrees well with overall mean values of γ(max), γ(avg) and γ% ≤ 1 at 2.02, 0.24 and 99.43%, respectively. γ(max) value was lower in 15 MV compared to 6 MV IMRT plan. Independent verification using MatriXX showed comparable overall mean values of γ(avg) and γ% ≤ 1 at 0.25 and 99.80%. However, in all plans, MatriXX showed significantly lower γ(max) (p < 0.05) with an overall mean value of 1.35. In portal dosimetry, compared to gamma values at 100 cm SDD, γ(max), γ(avg) and γ% ≤ 1 values improve from a mean of 0.16, 0.03 and 0.26 at 110 cm SDD to 0.35, 0.05 and 0.29 at 140 cm SDD. PD outcome was independent of gantry rotation. In conclusion, both MatriXX 2D ion chamber array and portal dosimetry showed comparable results and can be use as an alternative to each other for relative photon fluence verification.