Rectal deformation management with IGRT in prostate radiotherapy: Can it be managed with rigid alignment alone?

PURPOSE: It is challenging to achieve appropriate target coverage of the prostate with Image Guided Radiation Therapy (IGRT) while simultaneously constraining rectal doses within planned values when there is significant variability in rectal filling and shape. We investigated if rectum planning goals can be fulfilled using rigid CBCT-based on-board alignment to account for interfraction rectal deformations. METHODS: Delivered rectal doses corresponding to prostate alignment ("PR") and anterior rectum alignment ("AR") for 239 daily treatments from 13 patients are reported. Rectal doses were estimated by rigidly mapping the planned dose on the daily CT derived from the daily CBCT according to respective alignment shifts. Rectum V95% (rV95%) was used for analyses. RESULTS: Compared to "PR", "AR" alignment increased rV95% for an average of 34.4% across all patients. rV95% (cc) averaged over all fractions was significant from planning values for 10/13 patients for "PR" and for 9/13 for "AR". 3/13 patients had reproducible anatomy. Of patients with non-reproducible anatomy, three had dosimetrically more favorable, while seven had less favorable anatomies. Most shift differences (82.3%) between the "PR" and "AR" alignments larger than 2 mm resulted in rV95% changes larger than 2 cc. Most shift differences (82.2%) of 2 mm or less between the "PR" and "AR" alignments resulted in rV95% changes less than 2 cc. The average percentage of fractions among patients in which anterior or posterior shifts for "AR" and "PR" alignment was larger than the PTV margins was 9.1% (0.0%-37.5%) and 1.3% (0%-10%). CONCLUSION: Rectal deformation and subsequent inconsistent interfraction separation between prostate and rectal wall translate into anatomical changes that cannot always be mitigated with rigid alignment. If systematic differences exist due to a non-reproducible planning anatomy, attempts to restore the planned rectal doses through anterior rectum alignment produce rather small improvements and may result in unacceptable target underdosage.

Quantitative Analysis of Radiation Therapy-Induced Cardiac and Aortic Sequelae in Patients With Lung Cancer via Magnetic Resonance Imaging: A Pilot Study.

PURPOSE: The objective of this study was to quantify early radiation therapy (RT)-induced cardiac and aortic changes in patients with lung cancer using cardiac magnetic resonance imaging (MRI). METHODS AND MATERIALS: Nine patients with lung cancer treated with RT completed MR scans at baseline (before RT) and at 3 and 6 months after RT completion. Cine, T1/T2, late gadolinium enhancement (LGE), and 4-dimensional flow MRIs were acquired to assess biological and mechanical cardiovascular changes globally (ie, over the entire left ventricle (LV) or aorta) and regionally (according to an American Heart Association model). RESULTS: Regional metrics demonstrated multiple significant changes and dose-dependent responses. Notably, LGE showed changes at 3 and 6 months over septal and high-dose regions (P < .0458). Longitudinal strain changes were notable at septal and high-dose regions at 3 months and at septal regions at 6 months (P < .0469). Elevated T1/T2 signals (P < .0391) and changes in radial/circumferential strain at the septum (P < .0391) were observed at 3 months. Both T1/T2 signal and LGE were correlated with dose at 6 months (T1 signal also at 3 months), with significantly greater changes in regions receiving >50 Gy (P < .0331). LV dose was not correlated with LV strain changes (P > .1), but ascending aortic dose was correlated with strain changes at segments 1 and 2 of the LV (P < .0362). Global metrics identified only 2 significant responses: increase in LGE volume at 6 months and a reduction in ascending aortic circumferential strain at 3 months (P < .0356). CONCLUSIONS: Early MR-based changes after RT occurred primarily in high-dose regions and the LV septal wall. Although several early signals resolved by 6 months, LGE and longitudinal strain changes persisted for at least 6 months. Dose-dependent responses/correlations were observed for T1/T2/LGE changes at 6 months, with the greatest effect in regions exposed to >50 Gy. Further investigations with larger cohorts and longer follow-up are warranted to confirm regional dose dependence and the association between aortic dose and LV strain observed in this pilot study.

Institutional experience report on the target contouring workflow in the radiotherapy department for stereotactic arrhythmia radioablation delivered on conventional linear accelerators.

PURPOSE: In stereotactic arrhythmia radioablation (STAR), the target is defined using multiple imaging studies and a multidisciplinary team consisting of electrophysiologist, cardiologist, cardiac radiologist, and radiation oncologist collaborate to identify the target and delineate it on the imaging studies of interest. This report describes the workflow employed in our radiotherapy department to transfer the target identified based on electrophysiology and cardiology imaging to the treatment planning image set. METHODS: The radiotherapy team was presented with an initial target in cardiac axes orientation, contoured on a wideband late gadolinium-enhanced (WB-LGE) cardiac magnetic resonance (CMR) study, which was subsequently transferred to the computed tomography (CT) scan used for treatment planning-i.e., the average intensity projection (AIP) image set derived from a 4D CT-via an axial CMR image set, using rigid image registration focused on the target area. The cardiac and the respiratory motion of the target were resolved using ciné-CMR and 4D CT imaging studies, respectively. RESULTS: The workflow was carried out for 6 patients and resulted in an internal target defined in standard anatomical orientation that encompassed the cardiac and the respiratory motion of the initial target. CONCLUSION: An image registration-based workflow was implemented to render the STAR target on the planning image set in a consistent manner, using commercial software traditionally available for radiation therapy.

Quantitative assessment of radiotherapy-induced myocardial damage using MRI: a systematic review.

PURPOSE: To determine the role of magnetic resonance imaging (MRI)-based metrics to quantify myocardial toxicity following radiotherapy (RT) in human subjects through review of current literature. METHODS: Twenty-one MRI studies published between 2011-2022 were identified from available databases. Patients received chest irradiation with/without other treatments for various malignancies including breast, lung, esophageal cancer, Hodgkin's, and non-Hodgkin's lymphoma. In 11 longitudinal studies, the sample size, mean heart dose, and follow-up times ranged from 10-81 patients, 2.0-13.9 Gy, and 0-24 months after RT (in addition to a pre-RT assessment), respectively. In 10 cross-sectional studies, the sample size, mean heart dose, and follow-up times ranged from 5-80 patients, 2.1-22.9 Gy, and 2-24 years from RT completion, respectively. Global metrics of left ventricle ejection fraction (LVEF) and mass/dimensions of cardiac chambers were recorded, along with global/regional values of T1/T2 signal, extracellular volume (ECV), late gadolinium enhancement (LGE), and circumferential/radial/longitudinal strain. RESULTS: LVEF tended to decline at >20 years follow-up and in patients treated with older RT techniques. Changes in global strain were observed after shorter follow-up (13±2 months) for concurrent chemoradiotherapy. In concurrent treatments with longer follow-up (8.3 years), increases in left ventricle (LV) mass index were correlated with LV mean dose. In pediatric patients, increases in LV diastolic volume were correlated with heart/LV dose at 2 years post-RT. Regional changes were observed earlier post-RT. Dose-dependent responses were reported for several parameters, including: increased T1 signal in high-dose regions, a 0.136% increase of ECV per Gy, progressive increase of LGE with increasing dose at regions receiving >30 Gy, and correlation between increases in LV scarring volume and LV mean/V10/V25 Gy dose. CONCLUSION: Global metrics only detected changes over longer follow-up, in older RT techniques, in concurrent treatments, and in pediatric patients. In contrast, regional measurements detected myocardial damage at shorter follow-up and in RT treatments without concurrent treatment and had greater potential for dose-dependent response. The early detection of regional changes suggests the importance of regional quantification of RT-induced myocardial toxicity at early stages, before damage becomes irreversible. Further works with homogeneous cohorts are required to examine this matter.

Effects of respiratory and cardiac motion on estimating radiation dose to the left ventricle during radiotherapy for lung cancer.

PURPOSE: Establish a workflow to evaluate radiotherapy (RT) dose variation induced by respiratory and cardiac motion on the left ventricle (LV) and left ventricular myocardium (LVM). METHODS: Eight lung cancer patients underwent 4D-CT, expiratory T1-volumetric-interpolated-breath-hold-examination (VIBE), and cine MRI scans in expiration. Treatment plans were designed on the average intensity projection (AIP) datasets from 4D-CTs. RT dose from AIP was transferred onto 4D-CT respiratory phases. About 50% 4D-CT dose was mapped onto T1-VIBE (following registration) and from there onto average cine MRI datasets. Dose from average cine MRI was transferred onto all cardiac phases. Cumulative cardiac dose was estimated by transferring dose from each cardiac phase onto a reference cine phase following deformable image registration. The LV was contoured on each 4D-CT breathing phase and was called clinical LV (cLV); this structure is blurred by cardiac motion. Additionally, LV, LVM, and an American Heart Association (AHA) model were contoured on all cardiac phases. Relative maximum/mean doses for contoured regions were calculated with respect to each patient's maximum/mean AIP dose. RESULTS: During respiration, relative maximum and mean doses on the cLV ranged from -4.5% to 5.6% and -14.2% to 16.5%, respectively, with significant differences in relative mean doses between inspiration and expiration (P < 0.0145). During cardiac motion at expiration, relative maximum and mean doses on the LV ranged from 1.6% to 59.3%, 0.5% to 27.4%, respectively. Relative mean doses were significantly different between diastole and systole (P = 0.0157). No significant differences were noted between systolic, diastolic, or cumulative cardiac doses compared to the expiratory 4D-CT (P > 0.14). Significant differences were observed in AHA segmental doses depending on tumour proximity compared to global LV doses on expiratory 4D-CT (P < 0.0117). CONCLUSION: In this study, the LV dose was highest during expiration and diastole. Segmental evaluation suggested that future cardiotoxicity evaluations may benefit from regional assessments of dose that account for cardiopulmonary motion.

A comprehensive quality assurance procedure for 4D CT commissioning and periodic QA.

PURPOSE: The 4D computed tomography (CT) simulation is an essential procedure for tumors exhibiting breathing-induced motion. However, to date there are no established guidelines to assess the characteristics of existing systems and to describe meaningful performance. We propose a commissioning quality assurance (QA) protocol consisting of measurements and acquisitions that assess the mechanical and computational operation for 4D CT with both phase and amplitude-based reconstructions, for regular and irregular respiratory patterns. METHODS: The 4D CT scans of a QUASAR motion phantom were acquired for both regular and irregular breathing patterns. The hardware consisted of the Canon Aquilion Exceed LB CT scanner used in conjunction with the Anzai laser motion monitoring system. The nominal machine performance and reconstruction were demonstrated with measurements using regular breathing patterns. For irregular breathing patterns the performance was quantified through the analysis of the target motion in the superior and inferior directions, and the volume of the internal target volume (ITV). Acquisitions were performed using multiple pitches and the reconstructions were performed using both phase and amplitude-based binning. RESULTS: The target was accurately captured during regular breathing. For the irregular breathing, the measured ITV exceeded the nominal ITV parameters in all scenarios, but all deviations were less than the reconstructed slice thickness. The mismatch between the nominal pitch and the actual breathing rate did not affect markedly the size of the ITV. Phase and normalized amplitude binning performed similarly. CONCLUSIONS: We demonstrated a framework for measuring and quantifying the initial performance of 4D CT simulation scans that can also be applied during periodic QAs. The regular breathing provided confidence that the hardware and the software between the systems performs adequately. The irregular breathing data suggest that the system may be expected to capture in excess the target motion and geometry, but the deviation is expected to be within the slice thickness.

Quantitative assessment of intra- and inter-modality deformable image registration of the heart, left ventricle, and thoracic aorta on longitudinal 4D-CT and MR images.

PURPOSE: Magnetic resonance imaging (MRI)-based investigations into radiotherapy (RT)-induced cardiotoxicity require reliable registrations of magnetic resonance (MR) imaging to planning computed tomography (CT) for correlation to regional dose. In this study, the accuracy of intra- and inter-modality deformable image registration (DIR) of longitudinal four-dimensional CT (4D-CT) and MR images were evaluated for heart, left ventricle (LV), and thoracic aorta (TA). METHODS AND MATERIALS: Non-cardiac-gated 4D-CT and T1 volumetric interpolated breath-hold examination (T1-VIBE) MRI datasets from five lung cancer patients were obtained at two breathing phases (inspiration/expiration) and two time points (before treatment and 5 weeks after initiating RT). Heart, LV, and TA were manually contoured. Each organ underwent three intramodal DIRs ((A) CT modality over time, (B) MR modality over time, and (C) MR contrast effect at the same time) and two intermodal DIRs ((D) CT/MR multimodality at same time and (E) CT/MR multimodality over time). Hausdorff distance (HD), mean distance to agreement (MDA), and Dice were evaluated and assessed for compliance with American Association of Physicists in Medicine (AAPM) Task Group (TG)-132 recommendations. RESULTS: Mean values of HD, MDA, and Dice under all registration scenarios for each region of interest ranged between 8.7 and 16.8 mm, 1.0 and 2.6 mm, and 0.85 and 0.95, respectively, and were within the TG-132 recommended range (MDA < 3 mm, Dice > 0.8). Intramodal DIR showed slightly better results compared to intermodal DIR. Heart and TA demonstrated higher registration accuracy compared to LV for all scenarios except for HD and Dice values in Group A. Significant differences for each metric and tissue of interest were noted between Groups B and D and between Groups B and E. MDA and Dice significantly differed between LV and heart in all registrations except for MDA in Group E. CONCLUSIONS: DIR of the heart, LV, and TA between non-cardiac-gated longitudinal 4D-CT and MRI across two modalities, breathing phases, and pre/post-contrast is acceptably accurate per AAPM TG-132 guidelines. This study paves the way for future evaluation of RT-induced cardiotoxicity and its related factors using multimodality DIR.

Rigid and Deformable Image Registration for Radiation Therapy: A Self-Study Evaluation Guide for NRG Oncology Clinical Trial Participation.

PURPOSE: The registration of multiple imaging studies to radiation therapy computed tomography simulation, including magnetic resonance imaging, positron emission tomography-computed tomography, etc. is a widely used strategy in radiation oncology treatment planning, and these registrations have valuable roles in image guidance, dose composition/accumulation, and treatment delivery adaptation. The NRG Oncology Medical Physics subcommittee formed a working group to investigate feasible workflows for a self-study credentialing process of image registration commissioning. METHODS AND MATERIALS: The American Association of Physicists in Medicine (AAPM) Task Group 132 (TG132) report on the use of image registration and fusion algorithms in radiation therapy provides basic guidelines for quality assurance and quality control of the image registration algorithms and the overall clinical process. The report recommends a series of tests and the corresponding metrics that should be evaluated and reported during commissioning and routine quality assurance, as well as a set of recommendations for vendors. The NRG Oncology medical physics subcommittee working group found incompatibility of some digital phantoms with commercial systems. Thus, there is still a need to provide further recommendations in terms of compatible digital phantoms, clinical feasible workflow, and achievable thresholds, especially for future clinical trials involving deformable image registration algorithms. Nine institutions participated and evaluated 4 commonly used commercial imaging registration software and various versions in the field of radiation oncology. RESULTS AND CONCLUSIONS: The NRG Oncology Working Group on image registration commissioning herein provides recommendations on the use of digital phantom/data sets and analytical software access for institutions and clinics to perform their own self-study evaluation of commercial imaging systems that might be employed for coregistration in radiation therapy treatment planning and image guidance procedures. Evaluation metrics and their corresponding values were given as guidelines to establish practical tolerances. Vendor compliance for image registration commissioning was evaluated, and recommendations were given for future development.

Accreditation Program for Excellence (APEx): A Catalyst for Quality Improvement.

PURPOSE: In 2014 the American Society for Radiation Oncology's Accreditation Program for Excellence (APEx) was created in response to the Target Safely campaign. APEx is a powerful tool to measure and drive quality improvement in radiation oncology practices. METHODS AND MATERIALS: A task group from the American Society for Radiation Oncology's Practice Accreditation Committee was formed to provide an overview of the APEx accreditation program including analysis from specific program data. RESULTS: Through initiatives encouraged by the APEx program, participants are able to evaluate teamwork and effectiveness, implement documented procedures aimed at improving quality and safety, and establish quality management at the practice. The program's Self-Assessment measures performance with program requirements and indicates where compliance lacks standardization. Methods to address these deficiencies form part of on-going quality improvement. These quality outcomes promote the delivery of safe, high-quality care. CONCLUSION: The accreditation process through APEx is a commitment to an ongoing safety culture. Any worthwhile accreditation program should provide a meaningful assessment of practice operations, supply the tools to identify deficiencies and provide the opportunity to showcase growth and development. A commitment to completing APEx is a commitment to excellence for patients and all those who care for them.

Characterization of Respiration-Induced Motion in Prone Versus Supine Patient Positioning for Thoracic Radiation Therapy.

PURPOSE: Variations in the breathing characteristics, both on short term (intrafraction) and long term (interfraction) time scales, may adversely affect the radiation therapy process at all stages when treating lung tumors. Prone position has been shown to improve consistency (ie, reduced intrafraction variability) and reproducibility (ie, reduced interfraction variability) of the respiratory pattern with respect to breathing amplitude and period as a result of natural abdominal compression, with no active involvement required from the patient. The next natural step in investigating breathing-induced changes is to evaluate motion amplitude changes between prone and supine targets or organs at risk, which is the purpose of the present study. METHODS AND MATERIALS: Patients with lung cancer received repeat helical 4-dimensional computed tomography scans, one prone and one supine, during the same radiation therapy simulation session. In the maximum-inhale and maximum-exhale phases, all thoracic structures were delineated by an expert radiation oncologist. Geometric centroid trajectories of delineated structures were compared between patient orientations. Motion amplitude was measured as the magnitude of difference in structure centroid position between inhale and exhale. RESULTS: Amplitude of organ motion was larger when the patient was in the prone position compared with supine for all structures except the lower left lobe and left lung as a whole. Across all 12 patients, significant differences in mean motion amplitude between orientations were identified for the right lung (3.0 mm, P = .01), T2 (0.5 mm, P = .01) and T12 (2.1 mm, P < .001) vertebrae, the middle third of the esophagus (4.0 mm, P = .03), and the lung tumor (1.7 mm, P = .02). CONCLUSIONS: Respiration-induced thoracic organ motion was quantified in the prone position and compared with that of the supine position for 12 patients with thoracic lesions. The prone position induced larger organ motion compared with supine, particularly for the lung tumor, likely requiring increases in planning margins compared with supine.

Respiratory cycle characterization and optimization of amplitude-based gating parameters for prone and supine lung cancer patients.

The selection of posture between supine and prone induces changes in the characteristics of respiratory patterns in lung cancer patients. We characterize these differences, as well as introduce two new metrics to describe the quality of amplitude-based gating. The stability of the following metrics were measured for 134 supine-and-prone-paired individual breathing sessions from 22 patients: amplitude, period, inhale-to-exhale period ratio, and location of end-of-exhale and end-of-inhale peaks. A new normalization characteristic of typical amplitude was introduced for comparing patients based on external surrogates. This metric was used to characterize the baseline drift and to compare the overall gating efficiency between different amplitude-based gating parameters in a new proposed metric called the gating efficiency index. While the choice of supine or prone posture had negligible impact on the overall duty cycle or gating efficiency, some metrics showed greater difference, especially with prone showing reduced variability in period, inhale-to-exhale period ratio, amplitude, and relative amplitude of end-of-exhale. Therefore, the breathing pattern resulting from prone positioning was found to be more favorable due to less intrafraction variation. The gating efficiency index was used to quantitatively show that narrow amplitude gating windows near end-of-exhale have the best balance of decreased motion variability within gating while maintaining the longest duty cycle.

Deformable Registration for Dose Accumulation.

As deformable image registration makes its way into the clinical routine, the summation of doses from fractionated treatment regimens to evaluate cumulative doses to targets and healthy tissues is also becoming a frequently utilized tool in the context of image-guided adaptive radiotherapy. Accounting for daily geometric changes using deformable image registration and dose accumulation potentially enables a better understanding of dose-volume-effect relationships, with the goal of translation of this knowledge to personalization of treatment, to further enhance treatment outcomes. Treatment adaptation involving image deformation requires patient-specific quality assurance of the image registration and dose accumulation processes, to ensure that uncertainties in the 3D dose distributions are identified and appreciated from a clinical relevance perspective. While much research has been devoted to identifying and managing the uncertainties associated with deformable image registration and dose accumulation approaches, there are still many unanswered questions. Here, we provide a review of current deformable image registration and dose accumulation techniques, and related clinical application. We also discuss salient issues that need to be deliberated when applying deformable algorithms for dose mapping and accumulation in the context of adaptive radiotherapy and response assessment.

Evaluation of Image Registration Accuracy for Tumor and Organs at Risk in the Thorax for Compliance With TG 132 Recommendations.

PURPOSE: To evaluate accuracy for 2 deformable image registration methods (in-house B-spline and MIM freeform) using image pairs exhibiting changes in patient orientation and lung volume and to assess the appropriateness of registration accuracy tolerances proposed by the American Association of Physicists in Medicine Task Group 132 under such challenging conditions via assessment by expert observers. METHODS AND MATERIALS: Four-dimensional computed tomography scans for 12 patients with lung cancer were acquired with patients in prone and supine positions. Tumor and organs at risk were delineated by a physician on all data sets: supine inhale (SI), supine exhale, prone inhale, and prone exhale. The SI image was registered to the other images using both registration methods. All SI contours were propagated using the resulting transformations and compared with physician delineations using Dice similarity coefficient, mean distance to agreement, and Hausdorff distance. Additionally, propagated contours were anonymized along with ground-truth contours and rated for quality by physician-observers. RESULTS: Averaged across all patients, the accuracy metrics investigated remained within tolerances recommended by Task Group 132 (Dice similarity coefficient >0.8, mean distance to agreement <3 mm). MIM performed better with both complex (vertebrae) and low-contrast (esophagus) structures, whereas the in-house method performed better with lungs (whole and individual lobes). Accuracy metrics worsened but remained within tolerances when propagating from supine to prone; however, the Jacobian determinant contained regions with negative values, indicating localized nonphysiologic deformations. For MIM and in-house registrations, 50% and 43.8%, respectively, of propagated contours were rated acceptable as is and 8.2% and 11.0% as clinically unacceptable. CONCLUSIONS: The deformable image registration methods performed reliably and met recommended tolerances despite anatomically challenging cases exceeding typical interfraction variability. However, additional quality assurance measures are necessary for complex applications (eg, dose propagation). Human review rather than unsupervised implementation should always be part of the clinical registration workflow.