Evaluation and mitigation of deformable image registration uncertainties for MRI-guided adaptive radiotherapy.

PURPOSE: We evaluate the performance of a deformable image registration (DIR) software package in registering abdominal magnetic resonance images (MRIs) and then develop a mechanical modeling method to mitigate detected DIR uncertainties. MATERIALS AND METHODS: Three evaluation metrics, namely mean displacement to agreement (MDA), DICE similarity coefficient (DSC), and standard deviation of Jacobian determinants (STD-JD), are used to assess the multi-modality (MM), contour-consistency (CC), and image-intensity (II)-based DIR algorithms in the MIM software package, as well as an in-house developed, contour matching-based finite element method (CM-FEM). Furthermore, we develop a hybrid FEM registration technique to modify the displacement vector field of each MIM registration. The MIM and FEM registrations were evaluated on MRIs obtained from 10 abdominal cancer patients. One-tailed Wilcoxon-Mann-Whitney (WMW) tests were conducted to compare the MIM registrations with their FEM modifications. RESULTS: For the registrations performed with the MIM-CC, MIM-MM, MIM-II, and CM-FEM algorithms, their average MDAs are 0.62 ± 0.27, 2.39 ± 1.30, 3.07 ± 2.42, 1.04 ± 0.72 mm, and average DSCs are 0.94 ± 0.03, 0.80 ± 0.12, 0.77 ± 0.15, 0.90 ± 0.11, respectively. The p-values of the WMW tests between the MIM registrations and their FEM modifications are less than 0.0084 for STD-JDs and greater than 0.87 for MDA and DSC. CONCLUSIONS: Among the three MIM DIR algorithms, MIM-CC shows the smallest errors in terms of MDA and DSC but exhibits significant Jacobian uncertainties in the interior regions of abdominal organs. The hybrid FEM technique effectively mitigates the Jacobian uncertainties in these regions.

The AAPM/ASTRO 2023 Core Physics Curriculum for Radiation Oncology Residents.

PURPOSE: The American Association of Physicists in Medicine Radiation Oncology Medical Physics Education Subcommittee (ROMPES) has updated the radiation oncology physics core curriculum for medical residents in the radiation oncology specialty. METHODS AND MATERIALS: Thirteen physicists from the United States and Canada involved in radiation oncology resident education were recruited to ROMPES. The group included doctorates and master's of physicists with a range of clinical or academic roles. Radiation oncology physician and resident representatives were also consulted in the development of this curriculum. In addition to modernizing the material to include new technology, the updated curriculum is consistent with the format of the American Board of Radiology Physics Study Guide Working Group to promote concordance between current resident educational guidelines and examination preparation guidelines. RESULTS: The revised core curriculum recommends 56 hours of didactic education like the 2015 curriculum but was restructured to provide resident education that facilitates best clinical practice and scientific advancement in radiation oncology. The reference list, glossary, and practical modules were reviewed and updated to include recent literature and clinical practice examples. CONCLUSIONS: ROMPES has updated the core physics curriculum for radiation oncology residents. In addition to providing a comprehensive curriculum to promote best practice for radiation oncology practitioners, the updated curriculum aligns with recommendations from the American Board of Radiology Physics Study Guide Working Group. New technology has been integrated into the curriculum. The updated curriculum provides a framework to appropriately cover the educational topics for radiation oncology residents in preparation for their subsequent career development.

Development of a multi-layer quality assurance program to evaluate the uncertainty of deformable dose accumulation in adaptive radiotherapy.

PURPOSE: Deformable dose accumulation (DDA) has uncertainties which impede the implementation of DDA-based adaptive radiotherapy (ART) in clinic. The purpose of this study is to develop a multi-layer quality assurance (MLQA) program to evaluate uncertainties in DDA. METHODS: A computer program is developed to generate a pseudo-inverse displacement vector field (DVF) for each deformable image registration (DIR) performed in Accuray's PreciseART. The pseudo-inverse DVF is first used to calculate a pseudo-inverse consistency error (PICE) and then implemented in an energy and mass congruent mapping (EMCM) method to reconstruct a deformed dose. The PICE is taken as a metric to estimate DIR uncertainties. A pseudo-inverse dose agreement rate (PIDAR) is used to evaluate the consequence of the DIR uncertainties in DDA and the principle of energy conservation is used to validate the integrity of dose mappings. The developed MLQA program was tested using the data collected from five representative cancer patients treated with tomotherapy. RESULTS: DIRs were performed in PreciseART to generate primary DVFs for the five patients. The fidelity index and PICE of these DVFs on average are equal to 0.028 mm and 0.169 mm, respectively. With the criteria of 3 mm/3% and 5 mm/5%, the PIDARs of the PreciseART-reconstructed doses are 73.9 ± 4.4% and 87.2 ± 3.3%, respectively. The PreciseART and EMCM-based dose reconstructions have their deposited energy changed by 5.6 ± 3.9% and 2.6 ± 1.5% in five GTVs, and by 9.2 ± 7.8% and 4.7 ± 3.6% in 30 OARs, respectively. CONCLUSIONS: A pseudo-inverse map-based EMCM program has been developed to evaluate DIR and dose mapping uncertainties. This program could also be used as a sanity check tool for DDA-based ART.

Incorporating uncertainty bounds in daily deformable dose accumulation for adaptive radiation therapy of head-and-neck cancer.

BACKGROUND: The widespread use of deformable dose accumulation (DDA) in adaptive radiotherapy (ART) has been limited due to the lack of clinically compatible methods to consider its related uncertainties. PURPOSE: We estimate dose reconstruction uncertainties in daily DDA during CT-guided radiotherapy of head-and-neck cancer (HNC). We project confidence intervals of cumulative dose-volume parameters to the parotids and determine threshold values to guide clinical decision-making in ART. METHODS: Doses from daily images (megavoltage CTs [MVCTs]) of 20 HNC patients treated with tomotherapy were reconstructed and accumulated in the planning CT (PCT) utilizing a commercial DDA algorithm (PreciseART, Accuray, Inc.). For each mapped fraction, we warped the planning contours to the MVCT. Dose-volume histograms (DVHs) calculated in the MVCT (with warped contour and native dose) and the PCT (with native contour and mapped dose) were compared; the observed inconsistencies were associated with dose reconstruction errors. We derived uncertainty bounds for the transferred dose to voxels within the structure of interest in the PCT. The confidence intervals of cumulative dose-volume parameters were mid-treatment projected and evaluated as predictors of the end of treatment cumulative metrics. The need for plan adaptation was tested by comparing the projected uncertainty bounds with the treatment constraint points. RESULTS: Among all cases, the uncertainty in mean values of daily dose distributions mapped to the reference parotid's contours averaged between 2.8% and 3.8% of typical single fraction planning values and less than 1% for the planning target volume (PTV) D95%. These daily inconsistencies were higher in the ipsilateral compared to the contralateral parotid and increased toward the end of treatment. The magnitude of the uncertainty bounds for the cumulative treatment mean dose, D50%, and V20 Gy to the parotids, and PTV D95% were on average 3.5%, 6.6%, 4.6%, and 0.4% of the planned or prescribed values, with confidence intervals of 97.1%-107.0%, 98.2%-110.4%, 95.6%-111.1%, and 98.2%-100.2% respectively. The uncertainty intervals projected at mid-treatment intersected with the end of treatment bounds in 82% of the parotid's metrics; half of them presented an overlapping percentage greater than 60%. In five patients, the cumulative mean doses were projected at mid-treatment to exceed the total treatment constraint point by at least 3%; this threshold was exceeded at the end of treatment in the five cases. Underdosing was projected in only one case; the cumulative PTV D95% at the end of treatment was below the clinical threshold. CONCLUSION: Uncertainty bounds were incorporated into the results of a commercial DDA tool. The cohort's statistics showed that the parotids' cumulative DVH metrics frequently exceeded the planning values if confidence intervals were included. Most of the uncertainty bounds of the PTV metrics were kept within the clinical thresholds. We verified that mid-treatment violation projections led to exceeding the constraint point at the end of the treatment. Based on a 3% threshold, approximately one fourth of the patients are expected to be replanned at mid-treatment for parotids sparing during HNC radiotherapy.

Use of a DVH overlay technique for quality assurance of deformable image registration-based dose accumulation.

PURPOSE: We present a DVH overlay technique as a quality assurance (QA) metric for deformable image registration-based dose accumulation (DIR-DA). We use the technique to estimate the uncertainty in a DIR-DA for a revised treatment plan, and to compare two different DIR algorithms. MATERIALS AND METHODS: The required inputs to the DVH overlay workflow are deformably registered primary and secondary images, primary regions-of-interest (ROIs), and secondary dose distribution. The primary ROIs were forward warped to the secondary image, the secondary dose was inversely warped to the primary image, and the DVHs for each image were compiled. Congruent DVHs imply minimal inverse consistency error (ICE) within an ROI. For a pancreas case re-planned after 21 fractions of a 29-fraction course, the workflow was used to quantify dose accumulation error attributable to ICE, based on a hybrid contour-and-intensity-based DIR. The usefulness of the workflow was further demonstrated by assessing the performance of two DIR algorithms (one free-form intensity-based, FFIB, the other using normalized correlation coefficients, NCC, over small neighborhood patches) as applied toward kilovoltage computed tomography (kVCT)-to-megavoltage computed tomography (MVCT) registration and five-fraction dose accumulation of ten male pelvis cases. RESULTS: For the re-planned pancreas case, when applying the DVH-overlay-based uncertainties the resulting accumulated dose remained compliant with all but two of the original plan objectives. Among the male pelvis cases, FFIB and NCC DIR showed good invertibility within the planning target volume (PTV), according to the DVH overlay QA results. NCC DIR exhibited better invertibility for the bladder and rectum compared with FFIB. However, compared with FFIB, NCC DIR exhibited less regional deformation for the bladder and a tendency for increased local contraction of the rectum ROI. For the five-fraction summations, ICE for the PTV V100%Rx is comparable for both algorithms (FFIB 0.8 ± 0.7%, NCC 0.7 ± 0.3%). For the bladder and rectum V70%Rx , ICE is greater for FFIB (1.8 ± 0.7% for bladder, 1.7 ± 0.6% for rectum) than for NCC (1.0 ± 0.3% for bladder, 1.0 ± 0.4% for rectum). CONCLUSIONS: The DVH overlay technique identified instances in which a DIR exhibits favorable invertibility, implying low ICE in a DIR-based dose accumulation. Differences in the overlaid DVHs can also estimate dose accumulation errors attributable to ICE for given ROIs.

Clinical experience with planning, quality assurance, and delivery of burst-mode modulated arc therapy.

"Burst-mode" modulated arc therapy (hereafter referred to as "mARC") is a form of volumetric-modulated arc therapy characterized by variable gantry rotation speed, static MLCs while the radiation beam is on, and MLC repositioning while the beam is off. We present our clinical experience with the planning techniques and plan quality assurance measurements of mARC delivery. Clinical mARC plans for five representative cases (prostate, low-dose-rate brain, brain with partial-arc vertex fields, pancreas, and liver SBRT) were generated using a Monte Carlo-based treatment planning system. A conventional-dose-rate flat 6 MV and a high-dose-rate non-flat 7 MV beam are available for planning and delivery. mARC plans for intact-prostate cases can typically be created using one 360° arc, and treatment times per fraction seldom exceed 6 min using the flat beam; using the nonflat beam results in slightly higher MU per fraction, but also in delivery times less than 4 min and with reduced mean dose to distal organs at risk. mARC also has utility in low-dose-rate brain irradiation; mARC fields can be designed which deliver a uniform 20 cGy dose to the PTV in approximately 3-minute intervals, making it a viable alternative to conventional 3D CRT. For brain cases using noncoplanar arcs, delivery time is approximately six min using the nonflat beam. For pancreas cases using the nonflat beam, two overlapping 360° arcs are required, and delivery times are approximately 10 min. For liver SBRT, the time to deliver 800 cGy per frac-tion is at least 12 min. Plan QA measurements indicate that the mARC delivery is consistent with the plan calculation for all cases. mARC has been incorporated into routine practice within our clinic; currently, on average approximately 15 patients per day are treated using mARC; and with the exception of LDR brain cases, all are treated using the nonflat beam.

Comparing the quality of passively-scattered proton and photon tomotherapy plans for brain and head and neck disease sites.

We compare the quality of photon IMRT (helical tomotherapy) with classic proton plans for brain, head and neck tumors, in terms of target dose uniformity and conformity along with organ-at-risk (OAR) sparing. Plans were created for twelve target volumes among eight cases. All patients were originally planned and treated using helical tomotherapy. Proton plans were generated using a passively-scattered beam model with a maximum range of 32 g cm(-2) (225 MeV), range modulation in 0.5 g cm(-2) increments and range compensators with 4.8 mm milling tool diameters. All proton plans were limited to two to four beams. Plan quality was compared using uniformity index (UI), conformation number (CN) and a EUD-based plan quality index (fEUD). For 11 of the 12 targets, UI was improved for the proton plan; on average, UI was 1.05 for protons versus 1.08 for tomotherapy. For 7 of the 12 targets, the tomotherapy plan exhibited more favorable CN. For proximal OARs, the improved dose conformity to the target volume from tomotherapy led to a lower maximum dose. For distal OARs, the maximum dose was much lower for proton plans. For 6 of the 8 cases, near-total avoidance for distal OARs provided by protons leads to improved fEUD. However, if distal OARs are excluded in the fEUD calculation, the proton plans exhibit better fEUD in only 3 of the 8 cases. The distal OAR sparing and target dose uniformity are generally better with passive-scatter proton planning than with photon tomotherapy; proton therapy may be preferred if the clinician deems those attributes critical. However, tomotherapy may serve equally as well as protons for cases where superior target dose conformity from tomotherapy leads to plan quality nearly identical to or better than protons and for cases where distal OAR sparing is not concerning.

A phase I/II study piloting accelerated partial breast irradiation using CT-guided intensity modulated radiation therapy in the prone position.

BACKGROUND AND PURPOSE: External beam accelerated partial breast irradiation (EB-aPBI) is noninvasive with broader potential applicability than aPBI using brachytherapy. However, it has inherent challenges in daily reproducibility. Image-guide radiotherapy (IGRT) can improve daily reproducibility, allowing smaller treatment margins. Our institution proposed IG-IMRT in the prone position to evaluate dose homogeneity, conformality, normal tissue avoidance, and reliable targeting for EB-aPBI. We report preliminary results and toxicity from a phase I/II study evaluating the feasibility of EB-aPBI in the prone position using IG-IMRT. MATERIALS AND METHODS: Twenty post-menopausal women with node-negative breast cancer, excised tumors <3.0 cm, negative sentinel lymph node biopsy, and surgical clips demarcating the lumpectomy cavity underwent prone EB-aPBI using IG-IMRT on an IRB-approved phase I/II study. All patients underwent CT planning in the prone position. The lumpectomy cavity PTV represented a 2.0 cm expansion. 38.5 Gy was delivered in 10 fractions over 5 days, such that 95% of the prescribed dose covered >99% of the PTV. Dose constraints for the whole breast, lungs and heart were met. RESULTS: The median patient age was 61.5. Mean tumor size was 1.0 cm. 35% of patients had DCIS. Median PTV was 243 cc (108-530) and median breast reference volume was 1698 cc (647-3627). Average daily shifts for IGRT were (0.6, -4.6, 1.7 mm) with standard deviations of (6.3, 6.5, 6.4mm). Acute toxicity was G1 erythema in 80%, and G2 erythema, G2 fatigue, and G2 breast pain each occurred in 1 patient. With a median follow-up of 18.9 months (12-35), 40% of patients have G1 fibrosis and 30% have G1 hyperpigmentation. 95% of patients have good to excellent cosmesis. There have been no recurrences. CONCLUSIONS: These data demonstrate that EB-aPBI in the prone position using IG-IMRT is well tolerated, yields good dosimetric conformality, and results in promising early toxicity profiles.

A planning and delivery study of a rotational IMRT technique with burst delivery.

PURPOSE: A novel rotational IMRT (rIMRT) technique using burst delivery (continuous gantry rotation with beam off during MLC repositioning) is investigated. The authors evaluate the plan quality and delivery efficiency and accuracy of this dynamic technique with a conventional flat 6 MV photon beam. METHODS: Burst-delivery rIMRT was implemented in a planning system and delivered with a 160-MLC linac. Ten rIMRT plans were generated for five anonymized patient cases encompassing head and neck, brain, prostate, and prone breast. All plans were analyzed retrospectively and not used for treatment. Among the varied plan parameters were the number of optimization points, number of arcs, gantry speed, and gantry angle range (alpha) over which the beam is turned on at each optimization point. Combined rotational/step-and-shoot rIMRT plans were also created by superimposing multiple-segment static fields at several optimization points. The rIMRT trial plans were compared with each other and with plans generated using helical tomotherapy and VMAT. Burst-mode rotational IMRT plans were delivered and verified using a diode array, ionization chambers, thermoluminescent dosimeters, and film. RESULTS: Burst-mode rIMRT can achieve plan quality comparable to helical tomotherapy, while the former may lead to slightly better OAR sparing for certain cases and the latter generally achieves slightly lower hot spots. Few instances were found in which increasing the number of optimization points above 36, or superimposing step-and-shoot IMRT segments, led to statistically significant improvements in OAR sparing. Using an additional rIMRT partial arc yielded substantial OAR dose improvements for the brain case. Measured doses from the rIMRT plan delivery were within 4% of the plan calculation in low dose gradient regions. Delivery time range was 228-375 s for single-arc rIMRT 200-cGy prescription with a 300 MU/min dose rate, comparable to tomotherapy and VMAT. CONCLUSIONS: Rotational IMRT with burst delivery, whether combined with static fields or not, yields clinically acceptable and deliverable treatment plans.

Investigation of helical tomotherapy for partial-breast irradiation of prone-positioned patients.

PURPOSE: To investigate whether helical tomotherapy can provide conformal, uniform target-dose coverage for partial-breast irradiation (PBI) of patients positioned prone while achieving organ-at-risk sparing compliant with National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 guidelines; and to report our initial experience with the delivery of prone-breast PBI treatments using tomotherapy. METHODS AND MATERIALS: For our pilot study, we generated helical tomotherapy plans upon the images of 10 prone-positioned patients previously treated using conventional techniques. We also generated plans for 4 left-breast prone-positioned PBI patients who were treated using helical tomotherapy, and recalculated the planned sinograms upon the pretreatment megavoltage computed tomographic images. Of the planning target volume (PTV), 95% was prescribed to receive 38.5 Gy, administered twice daily for 5 days. RESULTS: For our pilot study, on average the maximum point dose to the PTV was 41.3 Gy, and 99% or more of the PTV received 90% or more of the prescribed dose. RTOG 0413 dose-volume histogram objectives were fulfilled for all organs at risk except the contralateral breast, which received a maximum point dose as high as 3.2 Gy in 1 case. For the prospective prone-positioned tomotherapy PBI plans, all objectives were met except the contralateral-breast maximum dose, which was 3.7 Gy on average. Dose calculation using the planned sinogram upon the pretreatment megavoltage computed tomographic images indicated consistency with the planned dose distributions. CONCLUSIONS: Helical tomotherapy can provide conformal and uniform target-dose coverage simultaneous with adequate sparing of critical structures; in this study only the contralateral breast dose exceeded RTOG 0413 guidelines. Dosimetric results for our 4 prospective patient cases were consistent with those for our 10-case pilot study.

A comparison of daily megavoltage CT and ultrasound image guided radiation therapy for prostate cancer.

In order to quantify the differences between ultrasound-imaging and megavoltage-CT (MVCT) daily prostate localization in prostate-cancer radiotherapy and their dosimetric impacts, daily shifts were analyzed for a total of 140 prostate cancer patients; 106 positioned using ultrasound-based imaging [B-mode Acquisition and Targeting (BAT)], and 34 using the MVCT from a TomoTherapy Hi-Art unit. The shifts indicated by the two systems were compared statistically along the right/left (R/L), superior/inferior (S/I), and anterior/posterior (A/P) directions. The systematic and random variations among the daily alignments were calculated. Margins to account for these shifts were estimated. The mean shifts and standard deviations along the R/L, S/I, and A/P directions were -0.11 +/- 3.80, 0.67 +/- 4.67, and 2.71+/- 6.31 mm for BAT localizations and -0.98 +/- 5.13, 0.27 +/- 3.35, and 1.00 +/- 4.22 mm for MVCT localizations, respectively. The systematic and random variations in daily shifts based on MVCT were generally smaller than those based on BAT, especially along the A/P direction. A t-test showed this difference to be statistically significant. The planning target volume margins in the A/P direction estimated to account for daily variations were 8.81 and 14.66 mm based on MVCT and BAT data, respectively. There was no statistically significant difference in the daily prostate movement pattern between the first few fractions and the remaining fractions. Dosimetric comparison of MVCT and BAT prostate alignments was performed for seven fractions from a patient. The degradation from the plan caused by the MVCT alignment is trivial, while that by BAT is substantial. The MVCT technique results in smaller variations in daily shifts than ultrasound imaging, indicating that MVCT is more reliable and precise for prostate localization. Ultrasound-based localization may overestimate the daily prostate motion, particularly in the A/P direction, negatively impacting prostate dose coverage and rectal sparing.

Correlation between internal fiducial tumor motion and external marker motion for liver tumors imaged with 4D-CT.

PURPOSE: We investigated the correlation between the motions of an external marker and internal fiducials implanted in the liver for 8 patients undergoing respiratory-based computed tomography (four-dimensional CT [4D-CT]) procedures. METHODS AND MATERIALS: The internal fiducials were gold seeds, 3 mm in length and 1.2 mm in diameter. Four patients each had one implanted fiducial, and the other four had three implanted fiducials. The external marker was a plastic box, which is part of the Real-Time Position Management System (RPM) used to track the patient's respiration. Each patient received a standard helical CT scan followed by a time-correlated CT-image acquisition (4D-CT). The 4D-CT images were reconstructed in 10 separate phases covering the entire respiratory cycle. RESULTS: The internal fiducial motion is predominant in the superior-inferior direction, with a range of 7.5-17.5 mm. The correlation between external respiration and internal fiducial motion is best during expiration. For 2 patients with their three fiducials separated by a maximum of 3.2 cm, the motions of the fiducials were well correlated, whereas for 2 patients with more widely spaced fiducials, there was less correlation. CONCLUSIONS: In general, there is a good correlation between internal fiducial motion imaged by 4D-CT and external marker motion. We have demonstrated that gating may be best performed at the end of the respiratory cycle. Special attention should be paid to gating for patients whose fiducials do not move in synchrony, because targeting on the correct respiratory amplitude alone would not guarantee that the entire tumor volume is within the treatment field.