A multimodality assessment of the protective capacity of statin therapy in a mouse model of radiation cardiotoxicity.

PURPOSE: Despite technological advances in radiotherapy (RT), cardiotoxicity remains a common complication in patients with lung, oesophageal and breast cancers. Statin therapy has been shown to have pleiotropic properties beyond its lipid-lowering effects. Previous murine models have shown statin therapy can reduce short-term functional effects of whole-heart irradiation. In this study, we assessed the efficacy of atorvastatin in protecting against the late effects of radiation exposure on systolic function, cardiac conduction, and atrial natriuretic peptide (ANP) following a clinically relevant partial-heart radiation exposure. MATERIALS AND METHODS: Female, 12-week old, C57BL/6j mice received an image-guided 16 Gy X-ray field to the base of the heart using a small animal radiotherapy research platform (SARRP), with or without atorvastatin from 1 week prior to irradiation until the end of the experiment. The animals were followed for 50 weeks with longitudinal transthoracic echocardiography (TTE) and electrocardiography (ECG) every 10 weeks, and plasma ANP every 20 weeks. RESULTS: At 30-50 weeks, mild left ventricular systolic function impairment observed in the RT control group was less apparent in animals receiving atorvastatin. ECG analysis demonstrated prolongation of components of cardiac conduction related to the heart base at 10 and 30 weeks in the RT control group but not in animals treated with atorvastatin. In contrast to systolic function, conduction disturbances resolved at later time-points with radiation alone. ANP reductions were lower in irradiated animals receiving atorvastatin at 30 and 50 weeks. CONCLUSIONS: Atorvastatin prevents left ventricular systolic dysfunction, and the perturbation of cardiac conduction following partial heart irradiation. If confirmed in clinical studies, these data would support the use of statin therapy for cardioprotection during thoracic radiotherapy.

Validation of a new open-source method for automatic delineation and dose assessment of the heart and LADCA in breast radiotherapy with simultaneous uncertainty estimation.

Radiotherapy has been shown to increase risks of cardiotoxicities for breast cancer patients. Automated delineation approaches are necessary for consistent and efficient assessment of cardiac doses in large, retrospective datasets, while patient-specific estimation of the uncertainty in these doses provides valuable additional data for modelling and understanding risks. In this work, we aim to validate the consistency of our previously described open-source software model for automatic cardiac delineation in the context of dose assessment, relative to manual contouring. We also extend our software to introduce a novel method to automatically quantify the uncertainty in cardiac doses based on expected inter-observer variability (IOV) in contouring. This method was applied to a cohort of 15 left-sided breast cancer patients treated in Denmark using modern tangential radiotherapy techniques. On each image set, the whole heart and left anterior descending coronary artery (LADCA) were contoured by nine independent experts; the range of doses to these nine volumes provided a reference for the dose uncertainties generated from the automatic method. Local and external atlas sets were used to test the method. Results give confidence in the consistency of automatic segmentations, with mean whole heart dose differences for local and external atlas sets of -0.20 ± 0.17 and -0.10 ± 0.14 Gy, respectively. Automatic estimates of uncertainties in doses are similar to those from IOV for both the whole heart and LADCA. Overall, this study confirms that our automated approach can be used to accurately assess cardiac doses, and the proposed method can provide a useful tool in estimating dose uncertainties.

An Assessment of Radiation Doses From Radon Exposures Using a Mouse Model System.

BACKGROUND: Radon and its progenies contribute significantly to the natural background radiation and cause several thousands of lung cancer cases per year worldwide. Moreover, patients with chronic inflammatory joint diseases are treated in radon galleries. Due to the complex nature of radon exposure, the doses associated with radon exposures are difficult to assess. Hence, there is a clear need to directly measure dose depositions from radon exposures to provide reliable risk estimates for radiation protection guidelines. OBJECTIVES: We aimed to assess tissue-specific radiation doses associated with radon activity concentrations, that deposit similar dose levels as the annual natural radon exposure or radon gallery visits. METHODS: We exposed mice to defined radon concentrations, quantified the number of 53BP1 foci as a measure of induced DNA damage, and compared it with the number of foci induced by known doses of reference-type radiations. An image-based analysis of the 3-dimensional foci pattern provided information about the radiation type inflicting the DNA damage. RESULTS: A 1-hour exposure to 440 kBq/m3 radon-induced DNA damage corresponding to a dose of ∼10 mGy in the lung and ∼3.3 mGy in the kidney, heart, and liver. A 1-hour exposure to 44 kBq/m3 provided values consistent with a linear relationship between dose and radon concentration. Two-thirds of the dose in the lung was caused by α-particles. The dose in the kidney, heart, and liver and one-third of the dose in the lung likely resulted from ß- and γ-rays. DISCUSSION: We found that radon exposures mainly lead to α-particle-induced DNA damage in the lung, consistent with the lung cancer risk obtained in epidemiologic studies. Our presented biodosimetric approach can be used to benchmark risk model calculations for radiation protection guidelines and can help to understand the therapeutic success of radon gallery treatments.

RETROSPECTIVE ASSESSMENT OF CLINICAL-MORPHOLOGICAL CHANGES OF THE HEPATOBILIARY SYSTEM IN LIVER CIRRHOSIS OF THE CHORNOBYL NPP ACCIDENT CLEAN-UP WORKERS. / RETROSPEKTYVNA OTsINKA KLINIKO-MORFOLOGIChNYKh ZMIN GEPATOBILIARNOÏ SYSTEMY PRY TsYROZI PEChINKY V UChASNYKIV LIKVIDATsIÏ NASLIDKIV ChORNOBYL'S'KOÏ KATASTROFY.

OBJECTIVE: to retrospectively characterize changes in the hepatobiliary system in liver cirrhosis (LC) in the clean-up workers of the Chornobyl NPP accident and to determine the factors of disease progression according to the expert materials of the Central Interagency Expert Commission on Establishing the Causal Relationship of the Diseases with the influence of factors of Chornobyl NPP accident. MATERIALS AND METHODS: Based on the data of 60 cases of the Central Interagency Expert Committee on establishing the causal link of diseases with the impact of the Chornobyl NPP accident, the factors of development, concomitant pathology and indicators of the hepatobiliary system status in 49 deceased and 11 alive clean-up workers with LC were investigated. RESULTS: A retrospective study of the morphological changes of the hepatobiliary system in the clean-up workers with LC showed that the main pathologic anatomical diagnosis in 37.8 % of cases was small-nodal LC, in 8.9 % - micromacronodular, in 4.4 % - large-nodal, in 2.2 % - primary biliary LC, in the other 40 % of cases - LC with uncer- tain nodal structure, as well as 2 (4.4 %) cases of fatty liver and 1 case (2.2 %) of portal cirrhosis against the back- ground of fatty liver. Pathomorphological changes were characterized by expressed growth of fibrous tissue with replacement of the liver parenchyma (fields of fibrosis), increase in size and impaired structure of the liver, thick- ening and tightening of its capsule, fibrotic changes in other organs - gastric mucosa, pancreas, spleen, lungs, heart. Histological examination revealed lobe structure abnormalities, false lobules, periportal fibrosis, lymphoid-lympho- cytic infiltration, diffuse fatty small-sized and large-drop dystrophy, and hepatocyte atrophy. Common inflammato- ry processes and fibrotic changes of other organs and systems: cardiovascular, urinary, bronchopulmonary, stomach, pancreas and spleen made the course of the LC more severe. The most frequent were cardiovascular diseases, signi- ficantly more frequent among the deceased than alive patients: hypertension - 67.3 % and 45.5 %, p < 0.05, coro- nary heart disease - 57.1 % and 18 %, p < 0.05. In most cases, the cause of death in the clean-up workers with LC was hepatic and cellular failure (53.3 %), which together with hepatic-renal failure (17.8 %) made 71.1 %. CONCLUSION: Changes in the hepatobiliary system of change in in the clean-up workers with LC were characterized by marked growth of fibrotic tissue with replacement of the parenchyma and impaired liver structure, fibrotic changes in other organs, diffuse fatty small and large droplet dystrophy and atrophy of hepatocytes. The severe course of the LC with the manifestation of the disease at the stage of decompensation was due to a vague clinical picture, lack of subjective symptoms of liver disease, slow, steadily progressing development, lack of or inadequate examination and treatment, a significant number of concomitant pathology of other organs and systems. The fac- tors of the development of LC in the clean-up workers were the long course of chronic liver disease, numerous con- comitant pathology, long stay in the accident zone, the effect of ionizing radiation, as well as the lack of dispensa- ry supervision and adequate treatment.

Practical Heart Sparing Breast Cancer Radiation Therapy Using Continuous Positive Airway Pressure (CPAP) in Resource-Limited Radiation Oncology Clinics.

PURPOSE: The purpose of this study was to report experiences of practical heart sparing breast radiation therapy (RT) using continuous positive airway pressure (CPAP) in resource-limited radiation oncology clinics. PATIENTS AND METHODS: Twelve patients underwent computed tomography-simulations with both free-breathing (FB) and CPAP under the individual maximum tolerable air pressure. For each patient, left-sided breast RT plans (9 with breast only, 3 with breast and regional nodal stations) with FB and CPAP were created using 3-dimensional conformal RT (supine tangential or wide tangential RT fields) according to RTOG 1304. For daily RT, patients started CPAP in the patients waiting area for 15 minutes before entering the treatment room and continued CPAP during RT. Treatment setup times between breast RT with and without CPAP were compared. RESULTS: All patients tolerated CPAP well with 8 to 15 cm H2O of air pressure. Compared with FB, CPAP inflated the thorax and increased total lung volume by 35±16% (CPAP: 3136±751 vs. FB: 2354±657 cm, P<0.01); caudally displaced the heart by 1.8 cm (P<0.01); and decreased heart volume within tangential RT fields on computed tomography-simulation scans by 96±4% (1.4±2.5 vs. 21±17 cm, P=0.02) in all patients. Planning target volume coverage was acceptable in all RT plans. CPAP lowered mean dose (Dmean) to heart by 47±22% (2.5±1.5 vs. 5.4±3.3 Gy, P<0.01); heart volume receiving ≥25 Gy (V25) by 82±18% (2.2±2.6 vs. 9.1±7.1%, P<0.01); Dmean to left anterior descending coronary artery by 68±8% (4.7±1.9 vs. 14.8±3.3 Gy, P<0.01). CPAP decreased radiation dose to ipsilateral lung compared with FB: 9.1±5.8 versus 11.2±8 Gy (20% reduction, P=0.03) of Dmean; 15.7±12.5 vs. 20.5±17.5% (25% reduction, P=0.03) of V20. RT with CPAP did not increase treatment setup time compared with FB (week 1: 362±63 vs. 352±77 s; week 2 to 5: 217±13 vs. 201±14 s, all P>0.25). CONCLUSION: Novel use of CPAP allowed efficient and practical heart sparing breast RT without increasing infrastructural requirements in resource-limited radiation oncology clinics.

Radiation damage studies in cardiac muscle cells and tissue using microfocused X-ray beams: experiment and simulation.

Soft materials are easily affected by radiation damage from intense, focused synchrotron beams, often limiting the use of scanning diffraction experiments to radiation-resistant samples. To minimize radiation damage in experiments on soft tissue and thus to improve data quality, radiation damage needs to be studied as a function of the experimental parameters. Here, the impact of radiation damage in scanning X-ray diffraction experiments on hydrated cardiac muscle cells and tissue is investigated. It is shown how the small-angle diffraction signal is affected by radiation damage upon variation of scan parameters and dose. The experimental study was complemented by simulations of dose distributions for microfocused X-ray beams in soft muscle tissue. As a simulation tool, the Monte Carlo software package EGSnrc was used that is widely used in radiation dosimetry research. Simulations also give additional guidance for a more careful planning of dose distribution in tissue.

Calculating organ and effective doses in paediatric interventional cardiac radiology based on DICOM structured reports - Is detailed examination data critical to dose estimates?

PURPOSE: To estimate effective dose (E), equivalent organ doses (HT) and associated conversion coefficients (CCE:KAP = E/KAP, CCHT:KAP = HT/KAP; KAP = Kerma-area product) in paediatric cardiac interventions, using detailed exposure data from radiation dose structured reports (RDSR). These "RDSR dose estimations" have been compared with estimations performed using the approach currently implemented in the clinic that is based on a simplified assumptions method (SAM). METHODS: The Monte Carlo system PCXMC, incorporated into a previously developed framework, was used to calculate E and HT for 202 children. The calculations were performed with input values from RDSR, and also using simplified assumptions, including fixed nominal values for the focus-skin distance, collimated beam size, irradiation geometry and patient size (age, weight and height). RESULTS: Mean HT to critical organs were: 5-25 mSv (lungs), 5-8 mSv (breasts) and 5-22 mSv (heart), with the lower and upper end of the doses associated with the neonatal and 15 years group, respectively. The associated mean CCHT:KAP for the different age groups were: 9.4-1.6 mSv/Gycm2 (lungs), 8.9-0.54 mSv/Gycm2 (breasts) and 9.3-1.4 mSv/Gycm2 (heart). CONCLUSIONS: The extension of the concept of a conversion coefficient for HT is introduced and CCHT:KAP values for paediatric cardiac interventions divided in age groups are presented. This method of linking the KAP to HT is intended for use in epidemiological/cohort studies or in clinics that do not have access to RDSR. Further, the population-averaged conversion coefficients for the critical organs estimated from RDSR, displayed no statistically significant difference compared with the SAM approach.

External beam accelerated partial breast irradiation: dosimetric assessment of conformal and three different intensity modulated techniques.

Background The aim of the study was to evaluate and compare four different external beam radiotherapy techniques of accelerated partial breast irradiation (APBI) considering target coverage, dose to organs at risk and overall plan quality. The investigated techniques were three dimensional conformal radiotherapy (3D-CRT), "step and shoot" (SS) and "sliding window" (SW) intensity-modulated radiotherapy (IMRT), intensity-modulated arc therapy (RA). Patients and methods CT scans of 40 APBI patients were selected for the study. The planning objectives were set up according to the international recommendations. Homogeneity, conformity and plan quality indices were calculated from volumetric and dosimetric parameters of target volumes and organs at risk. The total monitor units and feasibility were also investigated. Results There were no significant differences in the coverage of the target volume between the techniques. The homogeneity indices of 3D-CRT, SS, SW and RA plans were 0.068, 0.074, 0.058 and 0.081, respectively. The conformation numbers were 0.60, 0.80, 0.82 and 0.89, respectively. The V50% values of the ipsilateral breast for 3D-CRT, SS, SW and RA were 47.5%, 40.2%, 39.9% and 31.6%, respectively. The average V10% and V40% values of ipsilateral lung were 13.1%, 28.1%, 28%, 36% and 2.6%, 1.9%, 1.9%, 3%, respectively. The 3D-CRT technique provided the best heart protection, especially in the low dose region. All contralateral organs received low doses. The SW technique achieved the best plan quality index (PQI). Conclusions Good target volume coverage and tolerable dose to the organs at risk are achievable with all four techniques. Taking into account all aspects, we recommend the SW IMRT technique for APBI.

Comparative photon and proton dosimetry for patients with mediastinal lymphoma in the era of Monte Carlo treatment planning and variable relative biological effectiveness.

BACKGROUND: Existing pencil beam analytical (PBA) algorithms for proton therapy treatment planning are not ideal for sites with heterogeneous tissue density and do not account for the spatial variations in proton relative biological effectiveness (vRBE). Using a commercially available Monte Carlo (MC) treatment planning system, we compared various dosimetric endpoints between proton PBA, proton MC, and photon treatment plans among patients with mediastinal lymphoma. METHODS: Eight mediastinal lymphoma patients with both free breathing (FB) and deep inspiration breath hold (DIBH) CT simulation scans were analyzed. The original PBA plans were re-calculated with MC. New proton plans that used MC for both optimization and dose calculation with equivalent CTV/ITV coverage were also created. A vRBE model, which uses a published model for DNA double strand break (DSB) induction, was applied on MC plans to study the potential impact of vRBE on cardiac doses. Comparative photon plans were generated on the DIBH scan. RESULTS: Re-calculation of FB PBA plans with MC demonstrated significant under coverage of the ITV V99 and V95. Target coverage was recovered by re-optimizing the PT plan with MC with minimal change to OAR doses. Compared to photons with DIBH, MC-optimized FB and DIBH proton plans had significantly lower dose to the mean lung, lung V5, breast tissue, and spinal cord for similar target coverage. Even with application of vRBE in the proton plans, the putative increase in RBE at the end of range did not decrease the dosimetric advantages of proton therapy in cardiac substructures. CONCLUSIONS: MC should be used for PT treatment planning of mediastinal lymphoma to ensure adequate coverage of target volumes. Our preliminary data suggests that MC-optimized PT plans have better sparing of the lung and breast tissue compared to photons. Also, the potential for end of range RBE effects are unlikely to be large enough to offset the dosimetric advantages of proton therapy in cardiac substructures for mediastinal targets, although these dosimetric findings require validation with late toxicity data.

Assessment of a guideline-based heart substructures delineation in left-sided breast cancer patients undergoing adjuvant radiotherapy : Quality assessment within a randomized phase III trial testing a cardioprotective treatment strategy (SAFE-2014).

BACKGROUND AND PURPOSE: In our institute, breast cancer patients undergoing adjuvant treatment are included in a protocol aimed to reduce cardiovascular morbidity (SAFE-2014, NCT2236806), assessing preclinical heart damage with heart speckle-tracking ultrasound. To develop a dose constraint related to subclinical heart damage, a reliable delineation of heart substructures based on a pre-existing guideline was made. PATIENTS AND METHODS: Heart substructures of 16 left-sided breast cancer patients included in the SAFE protocol were delineated by five operators. For each substructure, a multi-contour delineation based on a majority vote algorithm (MCD) was created. A consensus-based delineation (CBD) was developed by an independent team of two blinded operators. Dice similarity coefficients (DSC) between volumes delineated by different operators and the MCD were collected and reported, as well as DSC between CBD and MCD. RESULTS: Mean DSCs between heart chambers delineated by each operator and the corresponding MCDs ranged between 0.78 and 0.96. Mean DSC between substructures delineated by all single operators and the corresponding MCD ranged between 0.84 and 0.94. Mean DSC between CBD and the corresponding MCD ranged from 0.89 to 0.97. CONCLUSION: Results showed low inter-observer variability of heart substructure delineation. This constitutes an external validation of the contouring atlas used, allowing a reliable dosimetric assessment of these volumes within the SAFE-2014 trial.

Heart toxicity from breast cancer radiotherapy : Current findings, assessment, and prevention.

BACKGROUND: Late cardiac toxicities caused by (particularly left-sided) breast radiotherapy (RT) are now recognized as rare but relevant sequelae, which has prompted research on risk structure identification and definition of threshold doses to heart subvolumes. The aim of the present review was to critically discuss the clinical evidence on late cardiac reactions based on dose-dependent outcome reports for mean heart doses as well as doses to cardiac substructures. METHODS: A literature review was performed to examine clinical evidence on radiation-induced heart toxicities. Mean heart doses and doses to cardiac substructures were focused upon based on dose-dependent outcome reports. Furthermore, an overview of radiation techniques for heart protection is given and non-radiotherapeutic aspects of cardiotoxicity in the multimodal setting of breast cancer treatment are discussed. RESULTS: Based on available findings, the DEGRO breast cancer expert panel recommends the following constraints: mean heart dose <2.5 Gy; DmeanLV (mean dose left ventricle) < 3 Gy; V5LV (volume of LV receiving ≥5 Gy) < 17%; V23LV (volume of LV receiving ≥23 Gy) < 5%; DmeanLAD (mean dose left descending artery) < 10 Gy; V30LAD (volume of LAD receiving ≥30 Gy) < 2%; V40LAD (volume of LAD receiving ≥40 Gy) < 1%. CONCLUSION: In addition to mean heart dose, breast cancer RT treatment planning should also include constraints for cardiac subvolumes such as LV and LAD. The given constraints serve as a clinicians' aid for ensuring adequate heart protection. The individual decision between sufficient protection of cardiac structures versus optimal target volume coverage remains in the physician's hand. The risk of breast cancer-specific mortality and a patient's cardiac risk factors must be individually weighed up against the risk of radiation-induced cardiotoxicity.

Automated Instead of Manual Treatment Planning? A Plan Comparison Based on Dose-Volume Statistics and Clinical Preference.

PURPOSE: Automated planning aims to speed up treatment planning and improve plan quality. We compared manual planning with automated planning for lung stereotactic body radiation therapy based on dose-volume histogram statistics and clinical preference. METHODS AND MATERIALS: Manual and automated intensity modulated radiation therapy plans were generated for 56 patients by use of software developed in-house and Pinnacle 9.10 Auto-Planning, respectively. Optimization times were measured in 10 patients, and the impact of the automated plan (AP) on the total treatment cost was estimated. For the remaining 46 patients, each plan was checked against our clinical objectives, and a pair-wise dose-volume histogram comparison was performed. Three experienced radiation oncologists evaluated each plan and indicated their preference. RESULTS: APs reduced the average optimization time by 77.3% but only affected the total treatment cost by 3.6%. Three APs and 0 manual plans failed our clinical objectives, and 13 APs and 9 manual plans showed a minor deviation. APs significantly reduced D2% (2% of the volume receives a dose of at least D2%) for the spinal cord, esophagus, heart, aorta, and main stem bronchus (P < .05) while preserving target coverage. The radiation oncologists found >75% of the APs clinically acceptable without any further fine-tuning. CONCLUSIONS: APs may help to create satisfactory treatment plans quickly and effectively. Because critical appraisal by qualified professionals remains necessary, there is no such thing as "fully automated" planning yet.

Assessment of deep inspiration breath hold (DIBH) amplitude and reduction in cardiac dose in left breast cancer patients.

INTRODUCTION: The primary aim of this study was to examine the impact of deep inspiration breath-hold (DIBH) amplitude on subsequent mean heart dose and V30 during radiotherapy. The secondary aim was to investigate if patient age influenced DIBH amplitude. METHOD: A retrospective study of 30 patients with left-sided breast cancer was completed. Patients were randomly selected from the total number of patients dual scanned in free breathing (FB) and DIBH over a 2-year period. Plans were retrospectively virtually simulated and statistical analysis performed. RESULTS: All patients achieved decreased V30 and mean cardiac dose using DIBH. A positive correlation was found between DIBH amplitude and cardiac V30 dose reduction (p = 0.007, R = 0.48). Ratio of amplitude increase from FB to DIBH and cardiac V30 reduction was positively correlated and statistically significant (p = 0.04, R = 0.38); Ratio of amplitude increase of at least 15 times FB achieved 100% V30 dose reduction, however this was also achieved with ratio increase as low as 6.25 times FB. A statistically significant positive correlation was identified between DIBH amplitude and mean cardiac dose reduction (p = 0.003, R = 0.523). No correlation was found between patient age and amplitude ratio increase (p = 0.602, R = -0.099). CONCLUSION: A 100% reduction in cardiac V30 can be achieved with a DIBH amplitude increase of 15 times FB. A full reduction can also be achieved at much lower levels (6.25 times FB in current study); however there appears to be no pre-determining patient factors to identify this. DIBH amplitudes of 1 cm-4 cm reduce cardiac mean dose by at least 50%.

A deep Boltzmann machine-driven level set method for heart motion tracking using cine MRI images.

Heart motion tracking for radiation therapy treatment planning can result in effective motion management strategies to minimize radiation-induced cardiotoxicity. However, automatic heart motion tracking is challenging due to factors that include the complex spatial relationship between the heart and its neighboring structures, dynamic changes in heart shape, and limited image contrast, resolution, and volume coverage. In this study, we developed and evaluated a deep generative shape model-driven level set method to address these challenges. The proposed heart motion tracking method makes use of a heart shape model that characterizes the statistical variations in heart shapes present in a training data set. This heart shape model was established by training a three-layered deep Boltzmann machine (DBM) in order to characterize both local and global heart shape variations. During the tracking phase, a distance regularized level-set evolution (DRLSE) method was applied to delineate the heart contour on each frame of a cine MRI image sequence. The trained shape model was embedded into the DRLSE method as a shape prior term to constrain an evolutional shape to reach the desired heart boundary. Frame-by-frame heart motion tracking was achieved by iteratively mapping the obtained heart contour for each frame to the next frame as a reliable initialization, and performing a level-set evolution. The performance of the proposed motion tracking method was demonstrated using thirty-eight coronal cine MRI image sequences.

In a Heartbeat: An Assessment of Dynamic Dose Variation to Cardiac Structures Using Dual Source Computed Tomography.

PURPOSE: To assess radiation dose variation to the left anterior descending artery (LAD), left main coronary artery (LMCA), left ventricle (LV), and whole heart (WH) during the cardiac cycle using dual source computed tomography (DSCT). METHODS AND MATERIALS: The present prospective study included patients with left-side breast cancer planned to undergo tangential radiation therapy. An electrocardiogram-synchronized contrast-injected DSCT scan was obtained with the patient in the treatment position, in deep-inspiration breath-hold, using retrospective sequential acquisition. The WH, LV, LMCA, and proximal, middle, and distal LAD segments were contoured on each phase of the cardiac cycle. The maximum, minimum, and mean Hausdorff distance between each structure and the tangential fields was assessed in ventricular systole and diastole. Four-dimensional dose-volume histograms were used to compare the systolic and diastolic dosimetric data. RESULTS: Ten patients were enrolled. The average maximum, minimum, and mean Hausdorff distance variation from systole to diastole was ≤4 mm for the LV and LMCA and ≤3 mm for the WH and LAD segments. WH maximum dose and volume receiving 5 Gy were decreased in systole compared with diastole (42.9 Gy versus 44.5 Gy, P = .03, and 21.7 cm3 versus 27.7 cm3, P = .01), but the mean dose remained similar throughout the cycle. The maximum and mean dose to the distal LAD was 21.2 Gy versus 26.6 Gy (P = .005) and 8.6 Gy versus 13.2 Gy (P = .006) in systole versus diastole, respectively. The maximum and mean dose to the middle LAD was 18.4 Gy versus 25.1 Gy (P = .005) and 8.5 Gy versus 10.2 Gy in systole versus diastole (P = .005). The maximum dose to the LV was lower in systole than in diastole (21.5 Gy vs 26.7 Gy; P = .005). CONCLUSIONS: In addition to deep-inspiration breath-hold, systolic irradiation is associated with a reduction in dose to the LAD, LV, and WH. In addition to its potential use in radiation planning for cardiac gating, DSCT imaging can be used to help define a planning organ at risk volume for clinically important cardiac substructures.

15O-H2O PET/CT as a tool for the quantitative assessment of early post-radiotherapy changes of heart perfusion in breast carcinoma patients.

OBJECTIVE: Studies examining radiation-induced heart toxicity in breast cancer patients are inconclusive. The aim of this study was to prospectively and quantitatively asses myocardial blood flow (MBF) with, for the first time, 15O-H2O PET/CT as a marker of heart damage in irradiated breast cancer patients. METHODS: 15 breast cancer patients receiving intact breast or chest wall irradiation were included in the analysis (six with right-sided and nine with left-sided breast cancer). They underwent 15O-H2O PET/CT before radiotherapy (RT) and 2 and 8 months after RT. MBF was quantitatively assessed at rest and under stress conditions in 17 heart segments distinguished according to the American Ultrasound Association classification. Regional MBF values were derived in each of the coronary artery territories. RESULTS: MBF decreased in 53% and increased in 33% of cases 2 months after RT in both left-sided and right-sided breast cancer patients. Stress testing was more sensitive than at-rest testing, demonstrating decreased perfusion in the segments supplied by the left anterior descending coronary artery (LAD) [5.41 ± 1.74 vs 4.52 ± 1.82 ml (g*min)-1; p = 0.018], which persisted at 6 months [5.41 ± 1.74 vs 4.40 ± 1.38 ml (g*min)-1; p = 0.032] and a decrease in global heart perfusion [5.14 ± 1.49 vs 4.46 ± 1.73 ml (g*min)-1; p = 0.036]. A minimal radiation dose applied to the LAD correlated with MBF changes observed 2 months after RT (r = -0.57; p = 0.032). Radiological findings were not correlated with clinical symptoms of heart toxicity. CONCLUSION: 15O-H2O PET/CT is safe and effective for the early detection and quantitative analysis of subclinical post-RT changes in heart perfusion in breast cancer patients. The LV segments supplied by the LAD are the main site of MBF changes. A minimum radiation dose deposited in the LAD may be a predictor of radiation-induced heart toxicity. Advances in knowledge: This is the first time that 15O-H2O PET/CT has been used to assess MBF after RT and the first granular description of the distribution of blood flow changes after breast cancer RT.

Assessment of voluntary deep inspiration breath-hold with CINE imaging for breast radiotherapy.

Deep Inspiration Breath-Hold (DIBH) techniques for breast cancer radiation therapy (RT) have reduced cardiac dose compared to Free Breathing (FB). Recently, a voluntary deep inspiration breath-hold (vDIBH) technique was established using in-room lasers and skin tattoos to monitor breath-hold. An in-house quality assessment of positional reproducibility during RT delivery with vDIBH in patients with left-sided breast cancer was evaluated. The electronic portal imaging device (EPID) was used in cinematographic (CINE) mode to capture a sequence of images during beam delivery. Weekly CINE images were retrospectively assessed for 20 left-sided breast cancer patients receiving RT in vDIBH, and compared with CINE images of 20 patients treated in FB. The intra-beam motion was assessed and the distance from the beam central axis (CA) to the internal chest wall (ICW) was measured on each CINE image. These were then compared to the planned distance on digitally reconstructed radiograph (DRR). The maximum intra-beam motion for any one patient measurement was 0.30 cm for vDIBH and 0.20 cm for FB. The mean difference between the distance from the CA to ICW on DRR and the equivalent distance on CINE imaging (as treated) was 0.28 cm (SD 0.17) for vDIBH patients and 0.25 cm (SD 0.14) for FB patients (P = 0.458). The measured values were comparable for patients undergoing RT in vDIBH, and for those in FB. This quality assessment showed that using in-room lasers and skin tattoos to independently monitor breath-hold in vDIBH as detected by 'on-treatment' CINE imaging is safe and effective.

Assessment of concomitant versus sequential trastuzumab on radiation-induced cardiovascular toxicity.

There are limited data regarding effect of trastuzumab on radiation-induced cardiovascular toxicity when used sequentially or concomitantly. This experimental study aims to investigate effect of trastuzumab on radiation-induced cardiovascular toxicity with respect to the treatment sequence. One hundred and eight female Wistar albino rats were divided into six groups (G): G1 was control, G2 was trastuzumab, and G3 was radiotherapy (RT); G4 and G6 were sequential RT and trastuzumab; and G5 was concomitant RT and trastuzumab groups, respectively. Rats were killed at 6th h, 21st and 70th days after RT; thoracic aorta and heart samples were obtained. Transthoracic echocardiography and functional studies evaluating relaxation of thoracic aorta were performed. Subendothelial edema scores of thoracic aorta samples at 21st and 70th days were higher in RT groups (G3, G4, G5, and G6) ( p < 0.001). There was a deterioration of relaxation responses of thoracic aorta samples in RT groups ( p < 0.001). Cardiac fibrosis (CF) scores revealed detrimental effect of RT beginning from 6th h and trastuzumab from 21st day. RT groups showed further deterioration of CF at 70th day. Ejection fraction, left ventricular mass, and fractional shortening were significantly decreased in G4, G5, and G6. Trastuzumab may increase pathological damage in cardiovascular structures when used with RT regardless of timing.

Revision of orthovoltage chest wall treatment using Monte Carlo simulations.

PURPOSE: Given the high local control rates observed in breast cancer patients undergoing chest wall irradiation by kilovoltage x-rays, we aimed to revisit this treatment modality by accurate calculation of dose distributions using Monte Carlo simulation. METHODS AND MATERIAL: The machine components were simulated using the MCNPX code. This model was used to assess the dose distribution of chest wall kilovoltage treatment in different chest wall thicknesses and larger contour or fat patients in standard and mid sternum treatment plans. Assessments were performed at 50 and 100 cm focus surface distance (FSD) and different irradiation angles. In order to evaluate different plans, indices like homogeneity index, conformity index, the average dose of heart, lung, left anterior descending artery (LAD) and percentage target coverage (PTC) were used. Finally, the results were compared with the indices provided by electron therapy which is a more routine treatment of chest wall. RESULT: These indices in a medium chest wall thickness in standard treatment plan at 50 cm FSD and 15 degrees tube angle was as follows: homogeneity index 2.57, conformity index 7.31, average target dose 27.43 Gy, average dose of heart, lung and LAD, 1.03, 2.08 and 1.60 Gy respectively and PTC 11.19%. Assessments revealed that dose homogeneity in planning target volume (PTV) and conformity between the high dose region and PTV was poor. To improve the treatment indices, the reference point was transferred from the chest wall skin surface to the center of PTV. The indices changed as follows: conformity index 7.31, average target dose 60.19 Gy, the average dose of heart, lung and LAD, 3.57, 6.38 and 5.05 Gy respectively and PTC 55.24%. Coverage index of electron therapy was 89% while it was 22.74% in the old orthovoltage method and also the average dose of the target was about 50 Gy but in the given method it was almost 30 Gy. CONCLUSION: The results of the treatment study show that the optimized standard and mid sternum treatment for different chest wall thicknesses is with 50 cm FSD and zero (vertical) tube angle, while in large contour patients, it is with 100 cm FSD and zero tube angle. Finally, chest wall kilovoltage and electron therapies were compared, which revealed that electron therapy produces a better dose distribution than kilovoltage therapy.

Influence of monte carlo variance with fluence smoothing in VMAT treatment planning with Monaco TPS.

INTRODUCTION: The study aimed to investigate the interplay between Monte Carlo Variance (MCV) and fluence smoothing factor (FSF) in volumetric modulated arc therapy treatment planning by using a sample set of complex treatment planning cases and a X-ray Voxel Monte Carlo-based treatment planning system equipped with tools to tune fluence smoothness as well as MCV. MATERIALS AND METHODS: The dosimetric (dose to tumor volume, and organ at risk) and physical characteristic (treatment time, number of segments, and so on) of a set 45 treatment plans for all combinations of 1%, 3%, 5% MCV and 1, 3, 5 FSF were evaluated for five carcinoma esophagus cases under the study. RESULT: Increase in FSF reduce the treatment time. Variation of MCV and FSF gives a highest planning target volume (PTV), heart and lung dose variation of 3.6%, 12.8% and 4.3%, respectively. The heart dose variation was highest among all organs at risk. Highest variation of spinal cord dose was 0.6 Gy. CONCLUSION: Variation of MCV and FSF influences the organ at risk (OAR) doses significantly but not PTV coverage and dose homogeneity. Variation in FSF causes difference in dosimetric and physical parameters for the treatment plans but variation of MCV does not. MCV 3% or less do not improve the plan quality significantly (physical and clinical) compared with MCV greater than 3%. The use of MCV between 3% and 5% gives similar results as 1% with lesser calculation time. Minimally detected differences in plan quality suggest that the optimum FSF can be set between 3 and 5.