Omar El-Sherif

Stress Hypoperfusion and Tissue Injury in Hypertrophic Cardiomyopathy: Spatial Characterization Using High-Resolution 3-Tesla Magnetic Resonance Imaging

Background— Ischemia and tissue injury are common in patients with hypertrophic cardiomyopathy. Cardiovascular magnetic resonance imaging offers combined evaluations of each phenomenon at sufficiently high resolution to examine transmural spatial distribution. In this prospective cohort study, we examine the spatial distribution of stress perfusion abnormalities and tissue injury in patients with hypertrophic cardiomyopathy. Methods and Results— One hundred consecutive patients with hypertrophic cardiomyopathy underwent cardiovascular magnetic resonance imaging. Cine, stress perfusion, late gadolinium enhancement, and T2-weighted imaging techniques were used. Each was spatially coregistered according to predefined segmental and subsegmental models and was blindly analyzed for abnormalities using validated techniques. Spatial associations among stress perfusion, late gadolinium enhancement, and T2 imaging were made at segmental and subsegmental levels. Of the 100 patients studied, the phenotype was septal in 86 and apical in 14. Late gadolinium enhancement imaging was abnormal in 79 patients (79%). Eighty-six patients met prespecified safety criteria to undergo stress perfusion, and ischemia was identified in 46 patients (57%). T2 imaging was available in 81 patients and was abnormal in 19 (29%). The dominant distribution of all 3 findings was to segment with hypertrophy. Subsegmental analysis revealed geographic dominance of ischemia within the subendocardial zones. However, this zone was most commonly spared from late gadolinium enhancement and T2 abnormalities, typically seen in midwall and subepicardial zones. Conclusions— Inducible hypoperfusion is a common finding in hypertrophic cardiomyopathy and is typically identified within segments exhibiting imaging markers of tissue injury. However, the respective transmural dominance of these phenomena seems distinct. Alternate factors contributing to a regional susceptibility to tissue injury are deserving of further study.Background— Ischemia and tissue injury are common in patients with hypertrophic cardiomyopathy. Cardiovascular magnetic resonance imaging offers combined evaluations of each phenomenon at sufficiently high resolution to examine transmural spatial distribution. In this prospective cohort study, we examine the spatial distribution of stress perfusion abnormalities and tissue injury in patients with hypertrophic cardiomyopathy. Methods and Results— One hundred consecutive patients with hypertrophic cardiomyopathy underwent cardiovascular magnetic resonance imaging. Cine, stress perfusion, late gadolinium enhancement, and T2-weighted imaging techniques were used. Each was spatially coregistered according to predefined segmental and subsegmental models and was blindly analyzed for abnormalities using validated techniques. Spatial associations among stress perfusion, late gadolinium enhancement, and T2 imaging were made at segmental and subsegmental levels. Of the 100 patients studied, the phenotype was septal in 86 and apical in 14. Late gadolinium enhancement imaging was abnormal in 79 patients (79%). Eighty-six patients met prespecified safety criteria to undergo stress perfusion, and ischemia was identified in 46 patients (57%). T2 imaging was available in 81 patients and was abnormal in 19 (29%). The dominant distribution of all 3 findings was to segment with hypertrophy. Subsegmental analysis revealed geographic dominance of ischemia within the subendocardial zones. However, this zone was most commonly spared from late gadolinium enhancement and T2 abnormalities, typically seen in midwall and subepicardial zones. Conclusions— Inducible hypoperfusion is a common finding in hypertrophic cardiomyopathy and is typically identified within segments exhibiting imaging markers of tissue injury. However, the respective transmural dominance of these phenomena seems distinct. Alternate factors contributing to a regional susceptibility to tissue injury are deserving of further study.

Comprehensive dosimetric planning comparison for early-stage, non-small cell lung cancer with SABR: fixed-beam IMRT versus VMAT versus TomoTherapy.

Volumetric-modulated arc therapy (VMAT) is emerging as a leading technology in treating early-stage, non-small cell lung cancer (NSCLC) with stereotactic ablative radiotherapy (SABR). However, two other modalities capable of delivering intensity-modulated radiation therapy (IMRT) include fixed-beam and helical TomoTherapy (HT). This study aims to provide an extensive dosimetric comparison among these various IMRT techniques for treating early-stage NSCLC with SABR. Ten early-stage NSCLC patients were retrospectively optimized using three fixed-beam techniques via nine to eleven beams (high and low modulation step-and-shoot (SS), and sliding window (SW)), two VMAT techniques via two partial arcs (SmartArc (SA) and RapidArc (RA)), and three HT techniques via three different fan beam widths (1 cm, 2.5 cm, and 5 cm) for 80 plans total. Fixed-beam and VMAT plans were generated using flattening filter-free beams. SS and SA, HT treatment plans, and SW and RA were optimized using Pinnacle v9.1, Tomoplan v.3.1.1, and Eclipse (Acuros XB v11.3 algorithm), respectively. Dose-volume histogram statistics, dose conformality, and treatment delivery efficiency were analyzed. VMAT treatment plans achieved significantly lower values for contralateral lung V5Gy(p≤0.05) compared to the HT plans, and significantly lower mean lung dose (p<0.006) compared to HT 5 cm treatment plans. In the comparison between the VMAT techniques, a significant reduction in the total monitor units (p=0.05) was found in the SA plans, while a significant decrease was observed in the dose falloff parameter, D2cm, (p=0.05), for the RA treatments. The maximum cord dose was significantly reduced (p=0.017) in grouped RA&SA plans compared to SS. Estimated treatment time was significantly higher for HT and fixed-beam plans compared to RA&SA (p<0.001). Although, a significant difference was not observed in the RA vs. SA (p=0.393). RA&SA outperformed HT in all parameters measured. Despite an increase in dose to the heart and bronchus, this study demonstrates that VMAT is dosimetrically advantageous in treating early-stage NSCLC with SABR compared to fixed-beam, while providing significantly shorter treatment times. PACS number(s): 87.55.D, 87.55.dk, 87.55.kd.Volumetric‐modulated arc therapy (VMAT) is emerging as a leading technology in treating early‐stage, non‐small cell lung cancer (NSCLC) with stereotactic ablative radiotherapy (SABR). However, two other modalities capable of delivering intensity‐modulated radiation therapy (IMRT) include fixed‐beam and helical TomoTherapy (HT). This study aims to provide an extensive dosimetric comparison among these various IMRT techniques for treating early‐stage NSCLC with SABR. Ten early‐stage NSCLC patients were retrospectively optimized using three fixed‐beam techniques via nine to eleven beams (high and low modulation step‐and‐shoot (SS), and sliding window (SW)), two VMAT techniques via two partial arcs (SmartArc (SA) and RapidArc (RA)), and three HT techniques via three different fan beam widths (1 cm, 2.5 cm, and 5 cm) for 80 plans total. Fixed‐beam and VMAT plans were generated using flattening filter‐free beams. SS and SA, HT treatment plans, and SW and RA were optimized using Pinnacle v9.1, Tomoplan v.3.1.1, and Eclipse (Acuros XB v11.3 algorithm), respectively. Dose‐volume histogram statistics, dose conformality, and treatment delivery efficiency were analyzed. VMAT treatment plans achieved significantly lower values for contralateral lung V5Gy(p≤0.05) compared to the HT plans, and significantly lower mean lung dose (p<0.006) compared to HT 5 cm treatment plans. In the comparison between the VMAT techniques, a significant reduction in the total monitor units (p=0.05) was found in the SA plans, while a significant decrease was observed in the dose falloff parameter, D2cm, (p=0.05), for the RA treatments. The maximum cord dose was significantly reduced (p=0.017) in grouped RA&SA plans compared to SS. Estimated treatment time was significantly higher for HT and fixed‐beam plans compared to RA&SA (p<0.001). Although, a significant difference was not observed in the RA vs. SA (p=0.393). RA&SA outperformed HT in all parameters measured. Despite an increase in dose to the heart and bronchus, this study demonstrates that VMAT is dosimetrically advantageous in treating early‐stage NSCLC with SABR compared to fixed‐beam, while providing significantly shorter treatment times. PACS number(s): 87.55.D, 87.55.dk, 87.55.kd

Sci—Thur AM: YIS - 01: Dosimetric Analysis of Respiratory Induced Cardiac Intrafraction Motion in Left-sided Breast Cancer Radiotherapy

Introduction: Long-term cardiac side effects in left-sided breast cancer patients (BREL) after post-operative radiotherapy has become one of the most debated issues in radiation oncology. Through breathing-adapted radiotherapy the volume of the heart exposed to radiation can be significantly reduced by delivering the radiation only at the end of inspiration phase of the respiratory cycle, this is referred to as inspiration gating (IG). The purpose of this study is to quantify the potential reduction in cardiac exposure during IG compared to conventional BREL radiotherapy and to assess the dosimetric impact of cardiac motion due to natural breathing. Methods: 24 BREL patients treated with tangential parallel opposed photon beams were included in this study. All patients received a standard fast helical planning CT (FH-CT) and a 4D-CT. Treatment plans were created on the FH-CT using a clinical treatment planning system. The original treatment plan was then superimposed onto the end of inspiration CT and all 10 phases of the 4D-CT to quantify the dosimetric impact of respiratory motion and IG through 4D dose accumulation. Results: Through IG the mean dose to the heart, left ventricle, and left anterior descending artery (LAD) can be reduced in comparison to the clinical standard BREL treatment by as much as 8.39%, 10.11%, and 13.71% respectively (p < 0.05). Conclusion: Failure to account for respiratory motion can lead to under or overestimation in the calculated DVH for the heart, and its sub-structures. IG can reduce cardiac exposure especially to the LAD during BREL radiotherapy.

WE-FG-202-06: The Use of Hybrid PET MRI for Identifying the Presence of Cardiac Inflammation Following External Beam Irradiation

PURPOSE To monitor the evolution of radiation-induced cardiac inflammation in a canine model using hybrid positron emission tomography (PET/magnetic resonance imaging (MRI). METHODS Research ethics approval was obtained for a longitudinal imaging study of 5 canines after cardiac irradiation. Animals were imaged at baseline, 3 months, 6 months, and 12 months post cardiac irradiation using a hybrid PET-MRI system (Biograph mMR, Siemens Healthcare). The imaging protocol was designed to assess changes in cardiac inflammation using 18 F-fluorodeoxyglucose (18 F-FDG) PET tracer. In order to image cardiac inflammation, the normal myocardial uptake of glucose was suppressed prior to the injection of 18 F-FDG. The suppression of glycolysis was achieved through; fasting (16-21 hours prior to the start of imaging) and an intravenous injection of heparin immediately followed by a 20% lipid infusion 20 min prior to the injection of 18 F-FDG. The standard uptake value (SUV) obtained from 17 myocardial regions were used to compare FDG scans. All animals received a simulation CT scan (GE Medical Systems) for radiation treatment planning. Radiation treatment plans were created using the Pinncale3 treatment planning system (Philips Radiation Oncology Systems) and designed to resemble the typical cardiac exposure during left-sided breast cancer radiotherapy. Cardiac irradiations were performed in a single fraction using a TrueBeam linear accelerator (Varian Medical Systems). RESULTS The delivered dose (mean ± standard error) to heart, left ventricle, and left anterior descending artery were 1.7±0.1 Gy, 2.7±0.1 Gy, and 5.5±0.3 Gy respectively. At these doses, a significant increase in 18 F-FDG uptake within the entire heart relative to baseline (1.1±0.02 g/ml) uptake was observed. 18 F-FDG uptake at 3 months, 6 months, and 12 months post irradiation were 1.8±0.03 g/ml, 2.4±0.06 g/ml, and 2.6±0.11 g/ml respectively. CONCLUSION Low doses of limited cardiac irradiation show evidence of a persistent global inflammatory response that can be detected using 18 F-FDG PET imaging. This work was supported through the Translational Breast Cancer Studentship award, funded in part by the Breast Cancer Society of Canada. Additional financial support is provided by the London Regional Cancer Program Catalyst Grant and the Thames Valley Veterinary Services.

WE-AB-303-10: The Use of On-Board KV Imaging During Respiratory-Gated VMAT Delivery to Determine the Correlation and Phase Shift Between External Marker Motion and Internal Tumour Motion

Purpose: To determine the correlation between internal tumor motion and external surrogate motion and any potential phase shifts during respiratory-gated VMAT delivery using on-board kV imaging. Methods: A respiratory motion phantom was used to trace the motion of an internal target, embedded with a 3 cm moving target, and an external surrogate. On-board kV projections were acquired at 11 frames per second during VMAT delivery on a TrueBeam v.1.6 (Varian Medical Systems, Palo Alto, CA) operating in developer mode. Full motion encompassed treatment delivery using sinusoidal motion with 4 second period and 2 cm peak-to-peak amplitude, and real-patient breathing (RPB) motion was programmed to the phantom. Respiratory-gated treatment deliveries (30–60% gating window) on five additional RPB waveforms were programmed to investigate correlation within the gating window. To investigate the capability of during treatment kV imaging to detect phase shifts during gated delivery, a second phantom with independent motion was used. Eight controlled phase shifts in intervals of 0.4 seconds were added to the sinusoidal motion. For each phase shift, the Pearson linear correlation coefficient statistical test was performed for each set of respiratory traces. The phase shift was calculated by shifting the external trace, in time, until maximum correlation was obtained. Results: A strong internal and external correlation was obtained for both the free-breathing (sinusoidal R2=0.993 and RPB R2=0.990) and respiratory-gated cases (range from R2=0.986–0.996). There was no significant difference between the programmed shift and that acquired using on-board kV imaging (p=0.899, R-squared = 0.997). Conclusion: During treatment kV imaging has the capability to verify intrafractional anatomical position. It can be accurately used as a tool to quantify internal and external correlation, and determine phase shifts within the gating window, and ultimately, the accuracy of respiratory-gating treatment delivery.

Stress Hypoperfusion and Tissue Injury in Hypertrophic CardiomyopathyClinical Perspective: Spatial Characterization Using High-Resolution 3-Tesla Magnetic Resonance Imaging

Background— Ischemia and tissue injury are common in patients with hypertrophic cardiomyopathy. Cardiovascular magnetic resonance imaging offers combined evaluations of each phenomenon at sufficiently high resolution to examine transmural spatial distribution. In this prospective cohort study, we examine the spatial distribution of stress perfusion abnormalities and tissue injury in patients with hypertrophic cardiomyopathy. Methods and Results— One hundred consecutive patients with hypertrophic cardiomyopathy underwent cardiovascular magnetic resonance imaging. Cine, stress perfusion, late gadolinium enhancement, and T2-weighted imaging techniques were used. Each was spatially coregistered according to predefined segmental and subsegmental models and was blindly analyzed for abnormalities using validated techniques. Spatial associations among stress perfusion, late gadolinium enhancement, and T2 imaging were made at segmental and subsegmental levels. Of the 100 patients studied, the phenotype was septal in 86 and apical in 14. Late gadolinium enhancement imaging was abnormal in 79 patients (79%). Eighty-six patients met prespecified safety criteria to undergo stress perfusion, and ischemia was identified in 46 patients (57%). T2 imaging was available in 81 patients and was abnormal in 19 (29%). The dominant distribution of all 3 findings was to segment with hypertrophy. Subsegmental analysis revealed geographic dominance of ischemia within the subendocardial zones. However, this zone was most commonly spared from late gadolinium enhancement and T2 abnormalities, typically seen in midwall and subepicardial zones. Conclusions— Inducible hypoperfusion is a common finding in hypertrophic cardiomyopathy and is typically identified within segments exhibiting imaging markers of tissue injury. However, the respective transmural dominance of these phenomena seems distinct. Alternate factors contributing to a regional susceptibility to tissue injury are deserving of further study.Background— Ischemia and tissue injury are common in patients with hypertrophic cardiomyopathy. Cardiovascular magnetic resonance imaging offers combined evaluations of each phenomenon at sufficiently high resolution to examine transmural spatial distribution. In this prospective cohort study, we examine the spatial distribution of stress perfusion abnormalities and tissue injury in patients with hypertrophic cardiomyopathy. Methods and Results— One hundred consecutive patients with hypertrophic cardiomyopathy underwent cardiovascular magnetic resonance imaging. Cine, stress perfusion, late gadolinium enhancement, and T2-weighted imaging techniques were used. Each was spatially coregistered according to predefined segmental and subsegmental models and was blindly analyzed for abnormalities using validated techniques. Spatial associations among stress perfusion, late gadolinium enhancement, and T2 imaging were made at segmental and subsegmental levels. Of the 100 patients studied, the phenotype was septal in 86 and apical in 14. Late gadolinium enhancement imaging was abnormal in 79 patients (79%). Eighty-six patients met prespecified safety criteria to undergo stress perfusion, and ischemia was identified in 46 patients (57%). T2 imaging was available in 81 patients and was abnormal in 19 (29%). The dominant distribution of all 3 findings was to segment with hypertrophy. Subsegmental analysis revealed geographic dominance of ischemia within the subendocardial zones. However, this zone was most commonly spared from late gadolinium enhancement and T2 abnormalities, typically seen in midwall and subepicardial zones. Conclusions— Inducible hypoperfusion is a common finding in hypertrophic cardiomyopathy and is typically identified within segments exhibiting imaging markers of tissue injury. However, the respective transmural dominance of these phenomena seems distinct. Alternate factors contributing to a regional susceptibility to tissue injury are deserving of further study.

Stress Hypoperfusion and Tissue Injury in Hypertrophic CardiomyopathyClinical Perspective

Background— Ischemia and tissue injury are common in patients with hypertrophic cardiomyopathy. Cardiovascular magnetic resonance imaging offers combined evaluations of each phenomenon at sufficiently high resolution to examine transmural spatial distribution. In this prospective cohort study, we examine the spatial distribution of stress perfusion abnormalities and tissue injury in patients with hypertrophic cardiomyopathy. Methods and Results— One hundred consecutive patients with hypertrophic cardiomyopathy underwent cardiovascular magnetic resonance imaging. Cine, stress perfusion, late gadolinium enhancement, and T2-weighted imaging techniques were used. Each was spatially coregistered according to predefined segmental and subsegmental models and was blindly analyzed for abnormalities using validated techniques. Spatial associations among stress perfusion, late gadolinium enhancement, and T2 imaging were made at segmental and subsegmental levels. Of the 100 patients studied, the phenotype was septal in 86 and apical in 14. Late gadolinium enhancement imaging was abnormal in 79 patients (79%). Eighty-six patients met prespecified safety criteria to undergo stress perfusion, and ischemia was identified in 46 patients (57%). T2 imaging was available in 81 patients and was abnormal in 19 (29%). The dominant distribution of all 3 findings was to segment with hypertrophy. Subsegmental analysis revealed geographic dominance of ischemia within the subendocardial zones. However, this zone was most commonly spared from late gadolinium enhancement and T2 abnormalities, typically seen in midwall and subepicardial zones. Conclusions— Inducible hypoperfusion is a common finding in hypertrophic cardiomyopathy and is typically identified within segments exhibiting imaging markers of tissue injury. However, the respective transmural dominance of these phenomena seems distinct. Alternate factors contributing to a regional susceptibility to tissue injury are deserving of further study.Background— Ischemia and tissue injury are common in patients with hypertrophic cardiomyopathy. Cardiovascular magnetic resonance imaging offers combined evaluations of each phenomenon at sufficiently high resolution to examine transmural spatial distribution. In this prospective cohort study, we examine the spatial distribution of stress perfusion abnormalities and tissue injury in patients with hypertrophic cardiomyopathy. Methods and Results— One hundred consecutive patients with hypertrophic cardiomyopathy underwent cardiovascular magnetic resonance imaging. Cine, stress perfusion, late gadolinium enhancement, and T2-weighted imaging techniques were used. Each was spatially coregistered according to predefined segmental and subsegmental models and was blindly analyzed for abnormalities using validated techniques. Spatial associations among stress perfusion, late gadolinium enhancement, and T2 imaging were made at segmental and subsegmental levels. Of the 100 patients studied, the phenotype was septal in 86 and apical in 14. Late gadolinium enhancement imaging was abnormal in 79 patients (79%). Eighty-six patients met prespecified safety criteria to undergo stress perfusion, and ischemia was identified in 46 patients (57%). T2 imaging was available in 81 patients and was abnormal in 19 (29%). The dominant distribution of all 3 findings was to segment with hypertrophy. Subsegmental analysis revealed geographic dominance of ischemia within the subendocardial zones. However, this zone was most commonly spared from late gadolinium enhancement and T2 abnormalities, typically seen in midwall and subepicardial zones. Conclusions— Inducible hypoperfusion is a common finding in hypertrophic cardiomyopathy and is typically identified within segments exhibiting imaging markers of tissue injury. However, the respective transmural dominance of these phenomena seems distinct. Alternate factors contributing to a regional susceptibility to tissue injury are deserving of further study.

Poster - Thur Eve - 63: Dosimetric impact of breathing motion in lung SBRT: Dual vs single volumetric modulated arc therapy

Volumetric modulated arc therapy (VMAT) is a time efficient treatment delivery platform capable of producing highly conformal dose distributions with a single 360° arc. However, additional arcs can be used to further improve the conformal dose distribution. For these reasons, VMAT is often used for stereotactic body radiation therapy (SBRT) in which the treatment deliveries are hypofractionated. The dosimetric impact of tumour motion, especially in lung SBRT where tumour motion is most significant and treatments are hypofractionated, has always been a clinical concern. Through the use of 4-dimensional computed tomography (4D-CT), 4D dose distributions can be calculated that account for dosimetric errors due to motion and temporal variation in lung density that are not accounted for in clinical treatment plans. The purpose of this study was to quantify the dosimetric differences that arise due to tumour motion and variations in lung density between single and dual VMAT SBRT treatment plans. Six patients previously treated for stage I/II non-small-cell lung cancer with SBRT were included in this retrospective study. 3D and 4D dose distributions were calculated for both single and dual arc plans for each of the six patients. Dose-volume histogram metrics are reported for the target and critical structures. The results show significant differences (p ≤ 0.05) between the 3D and 4D dose distributions for the ratio of the prescription isodose volume to the primary target volume (PTV). This result was consistent for both single and dual arc VMAT plans.

Poster — Thur Eve — 53: Analysis of the distribution of dose delivery during respiratory‐gated step‐and‐shoot IMRT for lung cancer radiotherapy

Respiratory motion is a large source of dosimetric error when treating lung cancer with Intensity Modulated Radiation Therapy (IMRT). The asynchronicity of the tumour motion and the multileaf collimator (MLC) used to modulate the radiation beam intensity, leads to the interplay effect. One method to account for this effect is respiratory gating. Treatment planning optimization for gated IMRT is performed on a subset average 4D-CT which includes the phases surrounding end exhalation. However, this assumes that the beam delivery will be evenly distributed amongst those phases. This study investigates the distribution of beam delivery during gated step-and-shoot IMRT (SS-IMRT) for both early and late stage non-small cell lung cancer (NSCLC). Four Stage I NSCLC patients, prescribed a dose of 54 Gy in 3 fractions, and five Stage III NSCLC patients, prescribed a dose of 60 Gy in 30 fractions, were retrospectively planned with high and low modulation beams-IMRT, and delivered using the QUASAR™ Programmable Respiratory Motion Platform with 15 mm and 20 mm peak-to-peak sinusoidal motion and real patient breathing motion. The percent monitor units delivered at each phase were compared. For Stage I patients, the monitor units delivered were evenly distributed over the gating window due to a high number of monitor units delivered per control point. For Stage III patients, as the complexity of SS-IMRT increases, there were more monitor units delivered in the initial gating phase. This dose discrepancy could potentially lead to geographic miss of the tumour and should be taken into account during treatment planning.