Habitat escalated adaptive therapy (HEAT): a phase 2 trial utilizing radiomic habitat-directed and genomic-adjusted radiation dose (GARD) optimization for high-grade soft tissue sarcoma.

BACKGROUND: Soft tissue sarcomas (STS), have significant inter- and intra-tumoral heterogeneity, with poor response to standard neoadjuvant radiotherapy (RT). Achieving a favorable pathologic response (FPR ≥ 95%) from RT is associated with improved patient outcome. Genomic adjusted radiation dose (GARD), a radiation-specific metric that quantifies the expected RT treatment effect as a function of tumor dose and genomics, proposed that STS is significantly underdosed. STS have significant radiomic heterogeneity, where radiomic habitats can delineate regions of intra-tumoral hypoxia and radioresistance. We designed a novel clinical trial, Habitat Escalated Adaptive Therapy (HEAT), utilizing radiomic habitats to identify areas of radioresistance within the tumor and targeting them with GARD-optimized doses, to improve FPR in high-grade STS. METHODS: Phase 2 non-randomized single-arm clinical trial includes non-metastatic, resectable high-grade STS patients. Pre-treatment multiparametric MRIs (mpMRI) delineate three distinct intra-tumoral habitats based on apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) sequences. GARD estimates that simultaneous integrated boost (SIB) doses of 70 and 60 Gy in 25 fractions to the highest and intermediate radioresistant habitats, while the remaining volume receives standard 50 Gy, would lead to a > 3 fold FPR increase to 24%. Pre-treatment CT guided biopsies of each habitat along with clip placement will be performed for pathologic evaluation, future genomic studies, and response assessment. An mpMRI taken between weeks two and three of treatment will be used for biological plan adaptation to account for tumor response, in addition to an mpMRI after the completion of radiotherapy in addition to pathologic response, toxicity, radiomic response, disease control, and survival will be evaluated as secondary endpoints. Furthermore, liquid biopsy will be performed with mpMRI for future ancillary studies. DISCUSSION: This is the first clinical trial to test a novel genomic-based RT dose optimization (GARD) and to utilize radiomic habitats to identify and target radioresistance regions, as a strategy to improve the outcome of RT-treated STS patients. Its success could usher in a new phase in radiation oncology, integrating genomic and radiomic insights into clinical practice and trial designs, and may reveal new radiomic and genomic biomarkers, refining personalized treatment strategies for STS. TRIAL REGISTRATION: NCT05301283. TRIAL STATUS: The trial started recruitment on March 17, 2022.

Essentially unedited deep-learning-based OARs are suitable for rigorous oropharyngeal and laryngeal cancer treatment planning.

Quality of organ at risk (OAR) autosegmentation is often judged by concordance metrics against the human-generated gold standard. However, the ultimate goal is the ability to use unedited autosegmented OARs in treatment planning, while maintaining the plan quality. We tested this approach with head and neck (HN) OARs generated by a prototype deep-learning (DL) model on patients previously treated for oropharyngeal and laryngeal cancer. Forty patients were selected, with all structures delineated by an experienced physician. For each patient, a set of 13 OARs were generated by the DL model. Each patient was re-planned based on original targets and unedited DL-produced OARs. The new dose distributions were then applied back to the manually delineated structures. The target coverage was evaluated with inhomogeneity index (II) and the relative volume of regret. For the OARs, Dice similarity coefficient (DSC) of areas under the DVH curves, individual DVH objectives, and composite continuous plan quality metric (PQM) were compared. The nearly identical primary target coverage for the original and re-generated plans was achieved, with the same II and relative volume of regret values. The average DSC of the areas under the corresponding pairs of DVH curves was 0.97 ± 0.06. The number of critical DVH points which met the clinical objectives with the dose optimized on autosegmented structures but failed when evaluated on the manual ones was 5 of 896 (0.6%). The average OAR PQM score with the re-planned dose distributions was essentially the same when evaluated either on the autosegmented or manual OARs. Thus, rigorous HN treatment planning is possible with OARs segmented by a prototype DL algorithm with minimal, if any, manual editing.

A head and neck treatment planning strategy for a CBCT-guided ring-gantry online adaptive radiotherapy system.

PURPOSE: A planning strategy was developed and the utility of online-adaptation with the Ethos CBCT-guided ring-gantry adaptive radiotherapy (ART) system was evaluated using retrospective data from Head-and-neck (H&N) patients that required clinical offline adaptation during treatment. METHODS: Clinical data were used to re-plan 20 H&N patients (10 sequential boost (SEQ) with separate base and boost plans plus 10 simultaneous integrated boost (SIB)). An optimal approach, robust to online adaptation, for Ethos-initial plans using clinical goal prioritization was developed. Anatomically-derived isodose-shaping helper structures, air-density override, goals for controlling hotspot location(s), and plan normalization were investigated. Online adaptation was simulated using clinical offline adaptive simulation-CTs to represent an on-treatment CBCT. Dosimetric comparisons were based on institutional guidelines for Clinical-initial versus Ethos-initial plans and Ethos-scheduled versus Ethos-adapted plans. Timing for five components of the online adaptive workflow was analyzed. RESULTS: The Ethos H&N planning approach generated Ethos-initial SEQ plans with clinically comparable PTV coverage (average PTVHigh V100%  = 98.3%, Dmin,0.03cc  = 97.9% and D0.03cc  = 105.5%) and OAR sparing. However, Ethos-initial SIB plans were clinically inferior (average PTVHigh V100%  = 96.4%, Dmin,0.03cc  = 93.7%, D0.03cc  = 110.6%). Fixed-field IMRT was superior to VMAT for 93.3% of plans. Online adaptation succeeded in achieving conformal coverage to the new anatomy in both SEQ and SIB plans that was even superior to that achieved in the initial plans (which was due to the changes in anatomy that simplified the optimization). The average adaptive workflow duration for SIB, SEQ base and SEQ boost was 30:14, 22.56, and 14:03 (min: sec), respectively. CONCLUSIONS: With an optimal planning approach, Ethos efficiently auto-generated dosimetrically comparable and clinically acceptable initial SEQ plans for H&N patients. Initial SIB plans were inferior and clinically unacceptable, but adapted SIB plans became clinically acceptable. Online adapted plans optimized dose to new anatomy and maintained target coverage/homogeneity with improved OAR sparing in a time-efficient manner.

Maintaining dosimetric quality when switching to a Monte Carlo dose engine for head and neck volumetric-modulated arc therapy planning.

Head and neck cancers present challenges in radiation treatment planning due to the large number of critical structures near the target(s) and highly heterogeneous tissue composition. While Monte Carlo (MC) dose calculations currently offer the most accurate approximation of dose deposition in tissue, the switch to MC presents challenges in preserving the parameters of care. The differences in dose-to-tissue were widely discussed in the literature, but mostly in the context of recalculating the existing plans rather than reoptimizing with the MC dose engine. Also, the target dose homogeneity received less attention. We adhere to strict dose homogeneity objectives in clinical practice. In this study, we started with 21 clinical volumetric-modulated arc therapy (VMAT) plans previously developed in Pinnacle treatment planning system. Those plans were recalculated "as is" with RayStation (RS) MC algorithm and then reoptimized in RS with both collapsed cone (CC) and MC algorithms. MC statistical uncertainty (0.3%) was selected carefully to balance the dose computation time (1-2 min) with the planning target volume (PTV) dose-volume histogram (DVH) shape approaching that of a "noise-free" calculation. When the hot spot in head and neck MC-based treatment planning is defined as dose to 0.03 cc, it is exceedingly difficult to limit it to 105% of the prescription dose, as we were used to with the CC algorithm. The average hot spot after optimization and calculation with RS MC was statistically significantly higher compared to Pinnacle and RS CC algorithms by 1.2 and 1.0 %, respectively. The 95% confidence interval (CI) observed in this study suggests that in most cases a hot spot of ≤107% is achievable. Compared to the 95% CI for the previous clinical plans recalculated with RS MC "as is" (upper limit 108%), in real terms this result is at least as good or better than the historic plans.

On the MLC leaves alignment in the direction orthogonal to movement.

The main focus of the recommended spatial accuracy tests for the multi-leaf collimators (MLC) is calibration of the leaf position along the movement direction and overall alignment to the radiation isocenter. No explicit attention was typically paid to the alignment of the leaves from the opposing banks in the direction orthogonal to movement. This paper is a case study demonstrating that verification of such alignment at the time of acceptance testing is prudent. The original standard MLC (SMLC) on an MRIdian MRI-guided linac (ViewRay Inc., Mountain View, CA, USA) was upgraded to a high-speed MLC (HSMLC), which is supposed to be mechanically identical to the SMLC except for the higher drive screw pitch. The results of the end-to-end IMRT tests demonstrated unacceptable dosimetric results exemplified by an average and maximum ion chamber (IC) point dose error in the high-dose low-gradient region of 2.5 ± 1.4% and 4.6%, respectively. Before the upgrade, those values were 0.3 ± 0.7% and 0.9%, respectively. An exhaustive analysis of possible failure modes eventually zeroed in on the average misalignment of about 1 mm in the Y (along the couch) direction between the right and left upper MLC banks. The MLC was replaced, reducing the Y-direction misalignment to 0.4 mm. As a result, the average and maximum IC dose-errors became acceptable 1.0 ± 0.7% and 1.6%, respectively. Simple film and/or chamber array tests during acceptance testing can easily detect Y-direction misalignments between opposing leaves banks measuring a fraction of a mm at isocenter. Left undetected, such misalignment can cause nontrivial dosimetric consequences.

Unlocking a closed system: dosimetric commissioning of a ring gantry linear accelerator in a multivendor environment.

The Halcyon™ platform is self-contained, combining a treatment planning (Eclipse) system TPS) with information management and radiation delivery components. The standard TPS beam model is configured and locked down by the vendor. A portal dosimetry-based system for patient-specific QA (PSQA) is also included. While ensuring consistency across the user base, this closed model may not be optimal for every department. We set out to commission independent TPS (RayStation 9B, RaySearch Laboratories) and PSQA (PerFraction, Sun Nuclear Corp.) systems for use with the Halcyon linac. The output factors and PDDs for very small fields (0.5 × 0.5 cm2 ) were collected to augment the standard Varian dataset. The MLC leaf-end parameters were estimated based on the various static and dynamic tests with simple model fields and honed by minimizing the mean and standard deviation of dose difference between the ion chamber measurements and RayStation Monte Carlo calculations for 15 VMAT and IMRT test plans. Two chamber measurements were taken per plan, in the high (isocenter) and lower dose regions. The ratio of low to high doses ranged from 0.4 to 0.8. All percent dose differences were expressed relative to the local dose. The mean error was 0.0 ± 1.1% (TG119-style confidence limit ± 2%). Gamma analysis with the helical diode array using the standard 3%Global/2mm criteria resulted in the average passing rate of 99.3 ± 0.5% (confidence limit 98.3%-100%). The average local dose error for all detectors across all plans was 0.2% ± 5.3%. The ion chamber results compared favorably with our recalculation with Eclipse and PerFraction, as well as with several published Eclipse reports. Dose distribution gamma analysis comparisons between RayStation and PerFraction with 2%Local/2mm criteria yielded an average passing rate of 98.5% ± 0.8% (confidence limit 96.9%-100%). It is feasible to use the Halcyon accelerator with independent planning and verification systems without sacrificing dosimetric accuracy.

Pretreatment CT and PET radiomics predicting rectal cancer patients in response to neoadjuvant chemoradiotherapy.

BACKGROUND: The purpose of this study was to characterize pre-treatment non-contrast computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (PET) based radiomics signatures predictive of pathological response and clinical outcomes in rectal cancer patients treated with neoadjuvant chemoradiotherapy (NACR T). MATERIALS AND METHODS: An exploratory analysis was performed using pre-treatment non-contrast CT and PET imaging dataset. The association of tumor regression grade (TRG) and neoadjuvant rectal (NAR) score with pre-treatment CT and PET features was assessed using machine learning algorithms. Three separate predictive models were built for composite features from CT + PET. RESULTS: The patterns of pathological response were TRG 0 (n = 13; 19.7%), 1 (n = 34; 51.5%), 2 (n = 16; 24.2%), and 3 (n = 3; 4.5%). There were 20 (30.3%) patients with low, 22 (33.3%) with intermediate and 24 (36.4%) with high NAR scores. Three separate predictive models were built for composite features from CT + PET and analyzed separately for clinical endpoints. Composite features with α = 0.2 resulted in the best predictive power using logistic regression. For pathological response prediction, the signature resulted in 88.1% accuracy in predicting TRG 0 vs. TRG 1-3; 91% accuracy in predicting TRG 0-1 vs. TRG 2-3. For the surrogate of DFS and OS, it resulted in 67.7% accuracy in predicting low vs. intermediate vs. high NAR scores. CONCLUSION: The pre-treatment composite radiomics signatures were highly predictive of pathological response in rectal cancer treated with NACR T. A larger cohort is warranted for further validation.

Comprehensive evaluation of the high-resolution diode array for SRS dosimetry.

A high-resolution diode array has been comprehensively evaluated. It consists of 1013 point diode detectors arranged on the two 7.7 × 7.7 cm2 printed circuit boards (PCBs). The PCBs are aligned face to face in such a way that the active volumes of all diodes are in the same plane. All individual correction factors required for accurate dosimetry have been validated for conventional and flattening filter free (FFF) 6MV beams. That included diode response equalization, linearity, repetition rate dependence, field size dependence, angular dependence at the central axis and off-axis in the transverse, sagittal, and multiple arbitrary planes. In the end-to-end tests the array and radiochromic film dose distributions for SRS-type multiple-target plans were compared. In the equalization test (180° rotation), the average percent dose error between the normal and rotated positions for all diodes was 0.01% ± 0.1% (range -0.3 to 0.4%) and -0.01% ± 0.2% (range -0.9 to 0.9%) for 6 MV and 6MV FFF beams, respectively. For the axial angular response, corrected dose stayed within 2% from the ion chamber for all gantry angles, until the beam direction approached the detector plane. In azimuthal direction, the device agreed with the scintillator within 1% for both energies. For multiple combinations of couch and gantry angles, the average percent errors were -0.00% ± 0.6% (range: -2.1% to 1.6%) and -0.1% ± 0.5% (range -1.6% to 2.1%) for the 6MV and 6MV FFF beams, respectively. The measured output factors were largely within 2% of the scintillator, except for the 5 mm 6MV beam showing a 3.2% deviation. The 2%/1 mm gamma analysis of composite SRS measurements produced the 97.2 ± 1.3% (range 95.8-98.5%) average passing rate against film. Submillimeter (≤0.5 mm) dose profile alignment with film was demonstrated in all cases.

A hybrid volumetric dose verification method for single-isocenter multiple-target cranial SRS.

A commercial semi-empirical volumetric dose verification system (PerFraction [PF], Sun Nuclear Corp.) extracts multi-leaf collimator positions from the electronic portal imaging device movies collected during a pre-treatment run, while the rest of the delivered control point information is harvested from the accelerator log files. This combination is used to reconstruct dose on a patient CT dataset with a fast superposition/convolution algorithm. The method was validated for single-isocenter multi-target SRS VMAT treatments against absolute radiochromic film measurements in a cylindrical phantom. The targets ranged in size from 0.8 to 3.6 cm and in number from 3 to 10 per plan. A total of 17 films rotated at different angles around the cylinder axis were analyzed. Each of 27 total targets was intercepted by at least one film, and 2-4 different films were analyzed per plan. Film dose was always scaled to the ion chamber measurement in a high-dose, low-gradient area deliberately created at the isocenter. The planar dose agreement between PF and film using 3%(Global dose-difference normalization)/1 mm gamma analysis was on average 99.2 ± 1.1%. The point dose difference in the low-gradient area in the middle of every target was below 3%, while PF-reconstructed and film dose centroids for individual targets showed submillimeter agreement when measured on a well aligned accelerator. Volumetrically, all voxels in all plans agreed between PF and the primary treatment planning system at the 3%/1 mm level. With proper understanding of its advantages and shortcomings, the tool can be applied to patient-specific QA in routine radiosurgical clinical practice.

Practical quantification of image registration accuracy following the AAPM TG-132 report framework.

The AAPM TG 132 Report enumerates important steps for validation of the medical image registration process. While the Report outlines the general goals and criteria for the tests, specific implementation may be obscure to the wider clinical audience. We endeavored to provide a detailed step-by-step description of the quantitative tests' execution, applied as an example to a commercial software package (Mirada Medical, Oxford, UK), while striving for simplicity and utilization of readily available software. We demonstrated how the rigid registration data could be easily extracted from the DICOM registration object and used, following some simple matrix math, to quantify accuracy of rigid translations and rotations. The options for validating deformable image registration (DIR) were enumerated, and it was shown that the most practically viable ones are comparison of propagated internal landmark points on the published datasets, or of segmented contours that can be generated locally. The multimodal rigid registration in our example did not always result in the desired registration error below ½ voxel size, but was considered acceptable with the maximum errors under 1.3 mm and 1°. The DIR target registration errors in the thorax based on internal landmarks were far in excess of the Report recommendations of 2 mm average and 5 mm maximum. On the other hand, evaluation of the DIR major organs' contours propagation demonstrated good agreement for lung and abdomen (Dice Similarity Coefficients, DSC, averaged over all cases and structures of 0.92 ± 0.05 and 0.91 ± 0.06, respectively), and fair agreement for Head and Neck (average DSC = 0.73 ± 0.14). The average for head and neck is reduced by small volume structures such as pharyngeal constrictor muscles. Even these relatively simple tests show that commercial registration algorithms cannot be automatically assumed sufficiently accurate for all applications. Formalized task-specific accuracy quantification should be expected from the vendors.

Superficial and peripheral dose in compensator-based FFF beam IMRT.

Flattening filter-free (FFF) beams produce higher dose rates. Combined with compensator-based intensity modulated radiotherapy (IMRT) techniques, the dose delivery for each beam can be much shorter compared to the flattened beam MLC-based or flattened beam compensator-based IMRT. This 'snap shot' IMRT delivery is beneficial to patients for tumor motion management. Due to softer energy, superficial doses in FFF beam treatment are usually higher than those from flattened beams. Due to no flattening filter, thus less photon scattering, peripheral doses are usually lower in FFF beam treatment. However, in compensator-based IMRT using FFF beams, the compensator is in the beam pathway. Does it introduce beam hardening effects and scattering such that the superficial dose is lower and peripheral dose is higher compared to FFF beam MLC-based IMRT? This study applied Monte Carlo techniques to investigate the superficial and peripheral doses in compensator-based IMRT using FFF beams and compared it to the MLC-based IMRT using FFF beams and flattened beams. Besides varying thicknesses of brass slabs to simulate varying thicknesses of compensators, a simple cone-shaped compensator was simulated to mimic a clinical application. The dose distribution in water phantom by the cone-shaped compensator was then simulated by multiple MLC-defined FFF and flattened beams with varying apertures. After normalization to the maximum dose, Dmax, the superficial and peripheral doses were compared between the FFF beam compensator-based IMRT and FFF/flattened beam MLC-based IMRT. The superficial dose at the central 0.5 mm depth was about 1% (of Dmax) lower in the compensator-based 6 MV FFF (6FFF) IMRT compared to the MLC-based 6FFF IMRT, and about 8% higher than the flattened 6 MV MLC-based IMRT dose. At 8 cm off-axis at depth of central maximum dose, dmax, the peripheral dose between the 6FFF and flattened 6 MV MLC demonstrated similar doses, while the compensator dose was about 1% (of Dmax) higher. Compensators reduce the superficial doses slightly compared to open FFF beams, but increases the peripheral doses due to scatter in the compensator.

Validation of a GPU-Based 3D dose calculator for modulated beams.

A superposition/convolution GPU-accelerated dose computation algorithm (the Calculator) has been recently incorporated into commercial software. The algorithm requires validation prior to clinical use. Three photon energies were examined: conventional 6 MV and 15 MV, and 10 MV flattening filter free (10 MVFFF). For a set of IMRT and VMAT plans based on four of the five AAPM Practice Guideline 5a downloadable datasets, ion chamber (IC) measurements were performed on the water-equivalent phantoms. The average difference between the Calculator and IC was -0.3 ± 0.8% (1SD). The same plans were projected on a phantom containing a biplanar diode array. We used the forthcoming criteria for routine gamma analysis, 3% dose-error (global (G) normalization, 2 mm distance to agreement, and 10% low dose cutoff). The γ (3%G/2 mm) average passing rate was 98.9 ± 2.1%. Measurement-guided three-dimensional dose reconstruction on the patient CT dataset (excluding the Lung) resulted in a similar average agreement rate with the Calculator: 98.2 ± 2.0%. The mean γ (3%G/2 mm) passing rate comparing the Calculator to the TPS (again excluding the Lung) was 99.0 ± 1.0%. Because of the significant inhomogeneity, the Lung case was investigated separately. The calculator has an alternate heterogeneity correction mode that can change the results in the thorax for higher-energy beams (15 MV). As this correction is nonphysical and was optimized for simple slab geometries, its application leads to mixed results when compared to the TPS and independent Monte Carlo calculations, depending on the CT dataset and the plan. The Calculator vs. TPS 15 MV Guideline 5a IMRT and VMAT plans demonstrate 96.3% and 93.4% γ (3%G/2 mm) passing rates respectively. For the lower energies, which should be predominantly used in the thoracic region, the passing rates for the same plans and criteria range from 98.6 to 100%. Overall, the Calculator accuracy is sufficient for the intended use.

Validation of an improved helical diode array and dose reconstruction software using TG-244 datasets and stringent dose comparison criteria.

The original helical ArcCHECK (AC) diode array and associated software for 3D measurement-guided dose reconstruction were characterized and validated; however, recent design changes to the AC required that the subject be revisited. The most important AC change starting in 2014 was a significant reduction in the overresponse of diodes to scattered radiation outside of the direct beam, accom-plished by reducing the amount of high-Z materials adjacent to the diodes. This change improved the diode measurement accuracy, but in the process invalidated the dose reconstruction models that were assembled based on measured data acquired with the older version of the AC. A correction mechanism was intro-duced in the reconstruction software (3DVH) to accommodate this and potential future design changes without requiring updating model parameters. For each permutation of AC serial number and beam model, the user can define in 3DVH a single correction factor which will be used to compensate for the difference in the out-of-field response between the new and original AC designs. The exact value can be determined by minimizing the dose-difference with an ionization chamber or another independent dosimeter. A single value of 1.17, corresponding to the maximum measured out-of-field response difference between the new and old AC, provided satisfactory results for all studied energies (6X, 15X, and flatten-ing filter-free 10XFFF). A library of standard cases recommended by the AAPM TG-244 Report was used for reconstructed dose verification. The overall difference between reconstructed dose and an ion chamber in a water-equivalent phantom in the targets was 0.0% ± 1.4% (1 SD). The reconstructed dose on a homogeneous phantom was also compared to a biplanar diode dosimeter (Delta4) using gamma analysis with 2% (local dose-error normalization) / 2 mm / 10% cutoff criteria. The mean agreement rate was 96.7% ± 3.7%. For the plans common with the previous comparison, the mean agreement rate was 98.3% ± 0.8%, essentially unchanged. We conclude that the proposed software modification adequately addresses the change in the dosimeter response.

Initial evaluation of automated treatment planning software.

Even with advanced inverse-planning techniques, radiation treatment plan opti-mization remains a very time-consuming task with great output variability, which prompted the development of more automated approaches. One commercially available technique mimics the actions of experienced human operators to pro-gressively guide the traditional optimization process with automatically created regions of interest and associated dose-volume objectives. We report on the initial evaluation of this algorithm on 10 challenging cases of locoreginally advanced head and neck cancer. All patients were treated with VMAT to 70 Gy to the gross disease and 56 Gy to the elective bilateral nodes. The results of post-treatment autoplanning (AP) were compared to the original human-driven plans (HDP). We used an objective scoring system based on defining a collection of specific dosimetric metrics and corresponding numeric score functions for each. Five AP techniques with different input dose goals were applied to all patients. The best of them averaged the composite score 8% lower than the HDP, across the patient population. The difference in median values was statistically significant at the 95% confidence level (Wilcoxon paired signed-rank test p = 0.027). This result reflects the premium the institution places on dose homogeneity, which was consistently higher with the HDPs. The OAR sparing was consistently better with the APs, the differences reaching statistical significance for the mean doses to the parotid glands (p < 0.001) and the inferior pharyngeal constrictor (p = 0.016), as well as for the maximum doses to the spinal cord (p = 0.018) and brainstem (p = 0.040). If one is prepared to accept less stringent dose homogeneity criteria from the RTOG 1016 protocol, nine APs would comply with the protocol, while providing lower OAR doses than the HDPs. Overall, AP is a promising clinical tool, but it could benefit from a better process for shifting the balance between the target dose coverage/homogeneity and OAR sparing.

Evaluation of the ΔV 4D CT ventilation calculation method using in vivo xenon CT ventilation data and comparison to other methods.

Ventilation distribution calculation using 4D CT has shown promising potential in several clinical applications. This study evaluated the direct geometric ventilation calculation method, namely the ΔV method, with xenon-enhanced CT (XeCT) ventilation data from four sheep, and compared it with two other published meth-ods, the Jacobian and the Hounsfield unit (HU) methods. Spearman correlation coefficient (SCC) and Dice similarity coefficient (DSC) were used for the evaluation and comparison. The average SCC with one standard deviation was 0.44 ± 0.13 with a range between 0.29 and 0.61 between the XeCT and ΔV ventilation distributions. The average DSC value for lower 30% ventilation volumes between the XeCT and ΔV ventilation distributions was 0.55 ± 0.07 with a range between 0.48 and 0.63. Ventilation difference introduced by deformable image registration errors improved with smoothing. In conclusion, ventilation distributions generated using ΔV-4D CT and deformable image registration are in reasonably agreement with the in vivo XeCT measured ventilation distribution.

Measurement-guided volumetric dose reconstruction for helical tomotherapy.

It was previously demonstrated that dose delivered by a conventional linear accelerator using IMRT or VMAT can be reconstructed - on patient or phantom datasets - using helical diode array measurements and a technique called planned dose perturbation (PDP). This allows meaningful and intuitive analysis of the agreement between the planned and delivered dose, including direct comparison of the dose-volume histograms. While conceptually similar to modulated arc techniques, helical tomotherapy introduces significant challenges to the PDP formalism, arising primarily from TomoTherapy delivery dynamics. The temporal characteristics of the delivery are of the same order or shorter than the dosimeter's update interval (50 ms). Additionally, the prevalence of often small and complex segments, particularly with the 1 cm Y jaw setting, lead to challenges related to detector spacing. Here, we present and test a novel method of tomotherapy-PDP (TPDP) designed to meet these challenges. One of the novel techniques introduced for TPDP is organization of the subbeams into larger subunits called sectors, which assures more robust synchronization of the measurement and delivery dynamics. Another important change is the optional application of a correction based on ion chamber (IC) measurements in the phantom. The TPDP method was validated by direct comparisons to the IC and an independent, biplanar diode array dosimeter previously evaluated for tomotherapy delivery quality assurance. Nineteen plans with varying complexity were analyzed for the 2.5 cm tomotherapy jaw setting and 18 for the 1 cm opening. The dose differences between the TPDP and IC were 1.0% ± 1.1% and 1.1% ± 1.1%, for 2.5 and 1.0 cm jaw plans, respectively. Gamma analysis agreement rates between TPDP and the independent array were: 99.1%± 1.8% (using 3% global normalization/3 mm criteria) and 93.4% ± 7.1% (using 2% global/2 mm) for the 2.5 cm jaw plans; for 1 cm plans, they were 95.2% ± 6.7% (3% G/3) and 83.8% ± 12% (2% G/2). We conclude that TPDP is capable of volumetric dose reconstruction with acceptable accuracy. However, the challenges of fast tomotherapy delivery dynamics make TPDP less precise than the IMRT/VMAT PDP version, particularly for the 1 cm jaw setting.

AAPM Medical Physics Practice Guideline 5.a.: Commissioning and QA of Treatment Planning Dose Calculations - Megavoltage Photon and Electron Beams.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education and professional practice of medical physics. The AAPM has more than 8,000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines:• Must and Must Not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline.• Should and Should Not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances.

Evaluation of semiempirical VMAT dose reconstruction on a patient dataset based on biplanar diode array measurements.

We report the results of a preclinical evaluation of recently introduced commercial tools for 3D patient IMRT/VMAT dose reconstruction, the Delta4 Anatomy calculation algorithm. Based on the same initial measurement, volumetric dose can be reconstructed in two ways. Three-dimensional dose on the Delta4 phantom can be obtained by renormalizing the planned dose distribution by the measurement values (D4 Interpolation). Alternatively, incident fluence can be approximated from the phantom measurement and used for volumetric dose calculation on an arbitrary (patient) dataset with a pencil beam algorithm (Delta4 PB). The primary basis for comparison was 3D dose obtained by previously validated measurement-guided planned dose perturbation method (ACPDP), based on the ArcCHECK dosimeter with 3DVH software. For five clinical VMAT plans, D4 Interpolation agreed well with ACPDP on a homogeneous cylindrical phantom according to gamma analysis with local dose-error normalization. The average agreement rates were 98.2% ± 1.3% (1 SD), (range 97.0%-100%) and 92.8% ± 3.9% (89.5%-99.2%), for the 3%/3 mm and 2%/2 mm criteria, respectively. On a similar geometric phantom, D4 PB demonstrated substantially lower agreement rates with ACPDP: 88.6% ± 6.8% (81.2%-96.1%) and 72.4% ± 8.4% (62.1%-81.1%), for 3%/3 mm and 2%/2 mm, respectively. The average agreement rates on the heterogeneous patients' CT datasets are lower yet: 81.2% ± 8.6% (70.4%-90.4%) and 64.6% ± 8.4% (56.5%-74.7%), respectively, for the same two criteria sets. For both threshold combinations, matched analysis of variance (ANOVA) multiple comparisons showed statistically significant differences in mean agreement rates (p < 0.05) for D4 Interpolation versus ACPDP on one hand, and D4 PB versus ACPDP on either cylindrical or patient dataset on the other hand. Based on the favorable D4 Interpolation results for VMAT plans, the resolution of the reconstruction method rather than hardware design is likely to be responsible for D4 PB limitations.

Novel Postoperative Hypofractionated Accelerated Radiation Dose-Painting Approach for Soft Tissue Sarcoma.

Purpose: Hypofractionated radiation therapy (RT) offers benefits in the treatment of soft tissue sarcomas (STS), including exploitation of the lower α/ß, patient convenience, and cost. This study evaluates the acute toxicity of a hypofractionated accelerated RT dose-painting (HARD) approach for postoperative treatment of STS. Methods and Materials: This is a retrospective review of 53 consecutive patients with STS who underwent resection followed by postoperative RT. Standard postoperative RT dosing for R0/R1/gross disease with sequential boost (50 Gy + 14/16/20 Gy in 32-35 fractions) were replaced with dose-painting, which adapts dose based on risk of disease burden, to 50.4 and 63, 64.4, 70 Gy in 28 fractions, respectively. The first 10 patients were replanned with a sequential boost RT approach and dosimetric indices were compared. Time-to-event outcomes, including local control, regional control, distant control, and overall survival, were estimated with Kaplan-Meier analysis. Results: Median follow-up was 25.2 months. Most patients had high-grade (59%) STS of the extremity (63%) who underwent resection with either R1 (40%) or close (36%) margins. Four patients experienced grade 3 acute dermatitis which resolved by the 3-month follow-up visit. The 2-year local control, regional control, distant control, and overall survival were 100%, 92%, 68%, and 86%, respectively. Compared with the sequential boost plan, HARD had a significantly lower field size (total V50 Gy; P = .002), bone V50 (P = .031), and maximum skin dose (P = .008). Overall treatment time was decreased by 4 to 7 fractions, which translated to a decrease in estimated average treatment cost of $3056 (range, $2651-$4335; P < .001). Conclusions: In addition to benefits in cost, convenience, and improved biologic effect in STS, HARD regimen offers a safe treatment approach with dosimetric advantages compared with conventional sequential boost, which may translate to improved long-term toxicity.

Novel Definitive Hypofractionated Accelerated Radiation Dose-painting (HARD) for Unresected Soft Tissue Sarcomas.

Purpose: Soft tissue sarcomas (STS) are historically radioresistant, with surgery being an integral component of their treatment. With their low α/ß, STS may be more responsive to hypofractionated radiation therapy (RT), which is often limited by long-term toxicity risk to surrounding normal tissue. An isotoxic approach using a hypofractionated accelerated radiation dose-painting (HARD) regimen allows for dosing based on clinical risk while sparing adjacent organs at risk. Methods and Materials: We retrospectively identified patients from 2019 to 2022 with unresected STS who received HARD with dose-painting to high, intermediate, and low-risk regions of 3.0 Gy, 2.5 Gy, and 2.0 to 2.3 Gy, respectively, in 20 to 22 fractions. Clinical endpoints included local control, locoregional control, progression free survival, overall survival, and toxicity outcomes. Results: Twenty-seven consecutive patients were identified and had a median age of 68 years and tumor size of 7.0 cm (range, 1.2-21.0 cm). Tumors were most often high-grade (70%), stage IV (70%), located in the extremities (59%), and locally recurrent (52%). With a median follow-up of 33.4 months, there was a 3-year locoregional control rate of 100%. The 3-year overall and progression-free survival were 44.9% and 23.3%, respectively. There were 5 (19%) acute and 2 (7%) late grade 3 toxicities, and there were no grade 4 or 5 toxicities at any point. Conclusions: The HARD regimen is a safe method of dose-escalating STS, with durable 3-year locoregional control. This approach is a promising alternative for unresected STS, though further follow-up is required to determine long-term control and toxicity.