Mean Left Anterior Descending Research Articles

Feasibility of Left Anterior Descending Coronary Artery Sparing Radiation Therapy for Locally Advanced Lung Cancer

Efforts to mitigate radiotherapy (RT) associated cardiotoxicity have focused on constraining mean heart dose (MHD). However, recent studies have shown greater predictive power with cardiac substructure dose metrics such as the left anterior descending (LAD) coronary artery volume (V) receiving 15Gy (V15Gy) ≥10%. Herein, we investigated the feasibility of LAD radiation sparing in contemporary IMRT/VMAT lung cancer plans. Single institution retrospective analysis of 54 locally advanced lung cancer patients treated with thoracic RT between February 2018-August 2021. After excluding 33 (5=non-IMRT/VMAT or intentionally LAD-optimized; 28=LAD V15Gy<10%), 21 plans with LAD V15Gy ≥10% were identified for LAD re-optimization with intent to meet LAD V15Gy <10% while maintaining meeting organ-at-risk (OAR) metrics and target coverage with original plan parameters. Dosimetric variables were compared using paired t tests. Most (57.1%, 12/21) were treated with definitive RT, 8/21 (38.1%) with post-operative RT, and one with neoadjuvant RT. The median prescribed RT dose was 60Gy (range 50.4-66Gy) in 30 fractions (range 28-33). LAD re-optimized plans (vs original) led to significant reductions in mean LAD V15Gy (39.4% ±13.9% vs 9.4% ±13.0%; p<0.001) and mean LAD dose (12.9Gy ± 4.6Gy vs 7.6Gy ±2.8Gy; p<0.001). Most (85.7%; 18/21) LAD re-optimized plans achieved LAD V15Gy <10%. There were no statistically significant differences in overall lung, esophageal, or spinal cord dose metrics. Only one re-optimization (1/21) exceeded an OAR constraint that was initially met in the original plan. To our knowledge, this is the first report describing the feasibility of LAD-optimized lung cancer RT planning using the newly identified LAD V15 Gy constraint. We observed that LAD V15Gy <10% is achievable in more than 85% of plans initially exceeding this constraint, with minimal dosimetric tradeoffs. Our results support the feasibility of routine incorporation of the LAD as an OAR in modern thoracic IMRT/VMAT planning.

Left Anterior Descending Coronary Artery-Optimized Knowledge-Based Radiotherapy Planning in Patients with Locally Advanced Non-Small Cell Lung Cancer

The left anterior descending (LAD) coronary artery volume receiving 15 Gy (V15 Gy) has been associated with major adverse cardiac events and mortality in patients with locally advanced non-small cell lung cancer (LA-NSCLC) treated with radiotherapy (RT). However, coronary arteries are not routinely contoured as standard-of-care and there is limited data describing coronary-sparing planning techniques. Our objective was to evaluate whether LAD-sparing could be improved compared to real-world plans using a commercial knowledge-based planning (KBP) software without clinically unacceptable tradeoffs to other critical organs at risk (OAR). Retrospective replanning analysis was conducted on 31 RT plans developed for patients with LA-NSCLC. Each case was manually replanned with volumetric modulated arc radiotherapy (VMAT) optimized for LAD V15 Gy sparing with a prescription dose of 60 Gy. The resulting plans were used to create an LAD-optimized KBP model. The model included both KBP-generated objectives and additional point objectives to meet LAD (V15 Gy < 10%), lung (V5 Gy < 60%, V20 < 30%, mean < 17 Gy), heart (mean < 20 Gy), spinal cord (D0.03cc < 45 Gy), esophagus (V60 Gy < 17%, mean < 34 Gy), and planning target volume (PTV; D95% = 100%). The LAD-optimized model was deployed to replan 33 additional VMAT plans for LA-NSCLC with prescription dose 60 Gy, delivered between 2018 and 2022. Dose constraints or objectives were only unmet with KBP when not met in the original plan. Descriptive statistics were used to compare dosimetric parameters between original and LAD-optimized KBP plans. For the 33 plans identified for LAD-optimized KBP replanning, the original plans had a mean LAD V15 Gy of 17.9% (standard error [SE], 3.9%), while the LAD-optimized KBP plans had a significantly lower mean LAD V15 Gy of 5.9% (SE, 1.9%; p = 0.031). There was no significant difference in mean heart dose between the original and LAD-optimized KBP plans (8.4 Gy [SE 6.6 Gy] vs. 7.3 Gy [SE 5.8 Gy]; p = 0.48). Of these 33 KBP plans, 42% (n = 14) had mean reductions in LAD V15 Gy from 40.5% (SE 4.3%) to 10.5% (SE 3.5%; p = 0.0002), with 9/14 now able to meet < 10%, without affecting other critical OAR objectives (p > 0.5 for lungs, esophagus, spinal cord). 45% (n = 15) originally had an LAD V15 Gy < 1%, which were unchanged using KBP (p > 0.3). Four plans (12%) had higher LAD V15 Gy in the KBP vs. original plan (2/4 still meeting < 10%), due to the model prioritizing other OARs to a greater degree. Improvements in LAD-sparing was achievable in more than 40% of plans without apparent clinically significant tradeoffs in other critical OARs and without corresponding change in MHD. This result underscores the importance of standard implementation of LAD contouring and dose constraints, particularly given the discordance between whole heart and LAD dose exposure.

Investigating the Impact of Coronary Artery Dosimetry on Major Adverse Cardiac Events after Thoracic Radiation Therapy

<h3>Purpose/Objective(s)</h3> Minimizing cardiac toxicity after thoracic radiation therapy (RT) remains a clinical challenge. Mean heart dose is associated with major adverse cardiac events (MACE) and recent studies suggest RT dose to coronary arteries may better quantify risk after conformal RT. Prior studies have not evaluated RT dose to individual coronary arteries in risk modeling. We therefore sought to develop an integrated dosimetric model accounting for RT doses received by each coronary artery. <h3>Materials/Methods</h3> We performed a retrospective study of a randomly selected representative cohort of patients with locally advanced non-small cell lung cancer. We scored cardiac events as (1) ischemic, (2) constrictive, (3) valvular, or (4) conductive. We contoured and measured doses received by the left circumflex (LCX), left anterior descending (LAD), left main coronary (LMCA), and right coronary arteries (RCA). RT doses were measured as equivalent dose in 2-Gray (Gy) fractions. Dosimetric parameters associated with cardiac toxicity were examined using cumulative incidence, competing risk regression models, receiver operator characteristic (ROC), and log-rank statistics with significance defined as two-tailed <i>P</i><0.05. <h3>Results</h3> We identified 100 patients who received definitive RT (median=66 Gy, range=60-74 Gy) from 2006-2020. Median follow-up was 4.1 years (range, 0-11.0). Median age was 70 years (range, 38-84). Half the cohort was male (50%), a majority had smoking history (81%), and all received chemotherapy (100%). Thirty (30%) experienced MACE at a median of 13 months post-RT. Most events were ischemic (n=17, 57%) or conductive (n=13, 43%), with only 3 cases (10%) of valvular disease. Mean heart, LCX, LAD, and LMCA doses were predictive of cardiac toxicity (AUC=0.59, 0.58, 0.59, and 0.63, respectively) and were each significantly associated with MACE on univariable analysis (<i>P</i><0.05). For patients with full labs available, 10-year atherosclerotic cardiovascular disease (ASCVD) risk was also associated with MACE (HR=1.31, <i>P</i>=0.04). Chemotherapy, age, diabetes, hypertension, prior cardiac event, and mean RCA dose were not associated with MACE. Using the log-rank statistic, we identified threshold mean doses of 1.82, 12.71, 15.45, and 31.29 Gy for the heart, LCX, LAD, and LMCA, respectively. Patients exceeding all three threshold doses to the LCX, LAD, and LMCA had a two-year rate of MACE of 57.1% versus 15.9% (<i>P</i>=0.005). On multivariable analysis after adjusting for ASCVD, patients exceeding all identified doses to the LCX, LAD, and LMCA were at nearly 5 times the risk of MACE (HR=4.76, <i>P</i>=0.0005). <h3>Conclusion</h3> Our results suggest that patients receiving doses above our identified thresholds to all of the left coronary arteries (LCX, LAD, and LMCA) are at highest risk of MACE. If validated, our findings may inform RT treatment planning, where sparing of at least one vessel may lead to lower risk of MACE.

Correlation of Left Anterior Descending Coronary Artery Radiation Dose with Major Adverse Cardiac Events and Feasibility of Coronary Artery Sparing Treatment Planning in Lung Cancer

<h3>Purpose/Objective(s)</h3> Radiation dose to the left anterior descending (LAD) coronary artery is associated with major adverse cardiac events (MACE) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). However, the newly identified LAD metric (percent volume receiving 15 Gy [LAD V15Gy]) has not been independently validated and the extent to which modern radiotherapy (RT) planning techniques can reduce LAD V15Gy without exceeding dose tolerances to other critical organs at risk (OAR) remains uncertain. <h3>Materials/Methods</h3> This is a single institution retrospective study of 98 patients with LA-NSCLC treated with RT between 2005-2020. The LAD was manually delineated for each patient. MACE (unstable angina, myocardial infarction, heart failure, coronary revascularization, and cardiac death) cumulative incidence was estimated and Fine and Gray regressions were performed, adjusting for non-cardiac death as a competing risk. Patients who received LAD V15Gy ≥10% and experienced MACE were re-planned with volumetric-modulated arc therapy (VMAT) to optimize reduction of LAD V15Gy while maintaining target coverage and meeting standard OAR constraints. <h3>Results</h3> The median follow up was 23.2 months. The median age was 69 years, 30.6% of patients had pre-existing coronary heart disease (CHD) or a CHD risk-equivalent. The mean LAD V15Gy was 32% (standard deviation [SD] 27.8%). Ten patients developed at least one MACE, with a 2-year cumulative incidence of 10.2% (95% CI: 3.1-17.0%). Adjusting for pre-existing CHD there was an increased risk of MACE with LAD V15Gy (subdistribution hazard ratio 1.03; 95% CI 1.00-1.06; p=.034), with a significant interaction between LAD V15Gy and CHD (p=.005). Among the 10 patients who developed a MACE, 6 (60%) had an LAD V15Gy ≥ 10% (mean 52%, range 10-100%). The original planning techniques included: 3-dimensional conformal RT (3D-CRT; n=2), static intensity-modulated RT (IMRT; n=2), and VMAT (n=2). In 4 of these plans (n=2 IMRT, n=1 3D-CRT, n=1 VMAT), the re-planned LAD V15Gy was reduced to <10%, however all 6/6 plans achieved some degree of LAD V15Gy reduction (range, 9-100%). Specifically, optimization with LAD-sparing VMAT achieved a mean absolute decrease of 35.1% for LAD V15Gy (SD 32.4%) and 6.2 Gy mean heart dose (SD 10.9 Gy), with a concomitant mean increase of 0.8 Gy mean lung dose (SD 1.8 Gy), and mean lung V20Gy of 0.2% (SD 4.1%). All re-plans achieved similar target coverage and remained within national guideline OAR constraints. <h3>Conclusion</h3> LAD V15Gy is associated with an increased risk of MACE in this independent retrospective cohort. VMAT-based LAD-sparing RT plan optimization is feasible and can achieve meaningful reductions in LAD V15Gy with potentially clinically acceptable tradeoffs in lung dose. Together, these findings underscore the need for more aggressive LAD-sparing RT planning approaches.

Accuracy of global longitudinal and territorial longitudinal strain in determining myocardial viability in out of window period Anterior wall myocardial infarction patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Primary percutaneous intervention remains the principal treatment modality for anterior wall myocardial infarction (AWMI). However, a large fraction of patients especially in the developing countries present outside the window period (OWP) with no chest pain and akinetic left anterior descending (LAD) territory on echocardiography. Revascularization in these patients is primarily guided by viability status. Purpose This study was conducted to determine the accuracy of strain echocardiographic parameters compared to single-photon emission computed tomography (SPECT) in predicting myocardial viability in patients of AWMI presenting OWP. Methods All patients presenting with AWMI-OWP without ongoing chest pain and akinetic LAD territory on echocardiography from December 2020 to June 2021 were recruited. All patients underwent determination of both Global longitudinal strain (GLS) and territorial longitudinal strain (TLS) within 24-72 hours on AWMI. In addition, all underwent SPECT to determine the percentage of non-viable myocardium. On SPECT, a defect &amp;gt;5% myocardial territory showing severe reperfusion defect was considered as a marker of non-viability. Results A total of 27 patients were recruited. The mean age of the population was 61.66 + 12.6 years. Acute left ventricular failure (LVF) and cardiogenic shock (CS) was present in 6 (22.2%) and 5 (18.5%) patients respectively. Out of 22 patients who underwent angiography, majority of the patients 19 (86%) had single vessel disease involving the LAD. The mean left ventricular ejection fraction (LVEF) of the study group was 29.6 + 6.5%. The mean GLS and LAD territory TLS of the study group was -11.13 + 3.14% and -7.2 + 2.75% respectively. On SPECT, 8 (29.6%) patients had non-viable underlying myocardium. Parameters that very significantly associated with non-viability on SPECT included past history of CAD (p = 0.004), smoking (p = 0.05) and presentation with LVF (p = 0.0008) and CS (p = 0.001). The mean LVEF was significantly lower in the group with non-viability on SPECT (32.3 + 5.1% vs 23.1 + 4.5%; p &amp;lt; 0.001). Both GLS (-12.8 + 1.4% vs -7.1+ 2.3%; p &amp;lt; 0.001) and TLS (-8.7 + 1.4% vs -3.8 + 1.8%; p &amp;lt; 0.001) were significantly lower in group showing non-viability on SPECT. On receiver operating curves, a GLS of &amp;gt; -10.45% and TLS of &amp;gt; -6.65%, both had a sensitivity of 87.5% and specificity of 89.5% in predicting non-viability on SPECT. Both showed good accuracy in predicting non-viability on overall quality model. (Figures 1 and 2) Conclusion Modalities like cardiac magnetic resonance, SPECT or positron emission tomography are resource dependent and take time to be performed. Hence, performing these investigations is challenging in unstable patients. Strain echocardiography provides GLS of the myocardium which has good sensitivity and specificity in predicting viability and can be performed safely and quickly in this high-risk group. Abstract Figure. Abstract Figure. Overall quality model

Impact of Cardiac Substructure Dosimetry on Late Cardiac Risk: A Report From the Childhood Cancer Survivor Study (CCSS)

<h3>Purpose/Objective(s)</h3> Prior estimates of radiation (RT)-associated cardiac disease risk in childhood cancer survivors are based on estimates of RT dose to the entire heart. We aimed to evaluate whether cardiac substructure RT dosimetry improves estimation of late cardiac disease risk. <h3>Materials/Methods</h3> We determined the cumulative incidence of CTCAE grade 3 – 5 cardiac disease (heart failure, coronary artery disease, valvular disease, arrhythmia, or pericardial disease) among 25,481 5-year survivors from CCSS diagnosed 1970 – 1999. Median age at diagnosis was 6.1 years (range 0 – 20) and at last follow-up was 29.8 years (5.6 – 65.9). We considered a single composite endpoint of any cardiac disease to best identify which substructures to prioritize for avoidance in RT planning to minimize the absolute risk of cardiac disease. We reconstructed RT fields for irradiated survivors (n = 12,228) on an age-scaled phantom and estimated mean RT dose to the heart, four chambers, four valves, and the left anterior descending (LAD), circumflex, main (LM), and right coronary arteries. Adjusted piecewise exponential models (including cumulative anthracycline dose) evaluated associations between mean RT dose to each structure and outcomes. Each substructure was individually added to a model with mean whole heart RT dose and the fit was assessed via the likelihood-ratio test to ascertain which substructures improved prediction of cardiac risk beyond whole heart dose. <h3>Results</h3> At 35 years from diagnosis, the cumulative incidence of any cardiac disease was 7.0% (95% CI 6.5 – 7.6). When adding each substructure separately to a model with mean whole heart dose, the addition of mean LAD (χ² = 29.1) or LM (χ² = 34.6) RT dose significantly improved the risk estimation of any cardiac disease (<i>P</i> < 0.01). Among survivors with mean whole heart doses < 10 Gy, increasing mean LAD but not mean LM doses significantly increased risk of late cardiac disease. Even among those with a mean heart dose of < 5 Gy, mean LAD dose of ≥10 Gy was associated with a more than three-fold increased risk of cardiac disease (Table 1). <h3>Conclusion</h3> Even among survivors with low mean heart doses (< 5 Gy), mean LAD doses ≥10 Gy increased risk of cardiac disease. Thus, for pediatric RT planning we recommend limiting mean LAD dose to < 10 Gy, even when mean heart dose constraints can be achieved. Table 1. Relative rate of grade 3 – 5 cardiac disease in childhood cancer survivors by RT dose to the heart and LAD.

Usefulness of Coronary Computed Tomographic Angiography to Evaluate Coronary Artery Disease in Radiotherapy-Treated Breast Cancer Survivors

Breast cancer is the most commonly diagnosed cancer in women and radiotherapy is a widely used treatment approach. However, there is an increased risk of coronary artery disease and cardiac death in women treated with radiotherapy. The present study was undertaken to clarify the relation between radiotherapy and coronary disease in women with previous breast irradiation using coronary computed tomographic angiography (CCTA). We conducted a retrospective analysis of women with a history of right or left-sided breast cancer (RBC; LBC) treated with radiotherapy who subsequently underwent CCTA. RBC patients who had reduced radiation doses to the myocardium served as controls. Patients (n = 6,593) with a history of nonmetastatic breast cancer treated with radiotherapy were screened for completion of CCTA; 49 LBC and 45 RBC women were identified. Age and risk factor matched patients with LBC had higher rates of coronary disease compared with RBC patients; left anterior descending (LAD) coronary artery (76% vs 31% [p < 0.001]), left circumflex (33% vs. 6.7% [p = 0.004]), and right coronary artery (37% vs 13% [p = 0.018]). Mean LAD radiation dose and mean heart dose strongly correlated with coronary disease, with a 21% higher incidence of disease in the LAD per Gy for mean LAD dose and a 95% higher incidence of disease in the LAD per Gy for mean heart dose. In conclusion, LBC patients treated with radiotherapy have a significantly higher incidence of coronary disease when compared with a matched group of patients treated for RBC. Radiation doses correlated with the incidence of coronary disease.

Evaluation of the morphological and clinical features of left anterior descending myocardial bridging with multi-detector computed tomography.

AimThe aim of the study was to assess the incidence, localization, depth, length of myocardial bridging (MB) with left anterior descending (LAD), systolic compression ratio, atherosclerotic plaque localization and degree of stenosis by 256-slice multi-detector computed tomography (MDCT).Material and methodsComputed tomography (CT) scans from a total of 3947 patients who underwent MDCT were reviewed retrospectively for LAD MB. A diastolic and systolic dataset with the best image quality was selected. Myocardial bridge was defined as a coronary artery with an intra-myocardial course. Myocardial bridging was divided into “deep” or “superficial”. The length and depth of the bridging segment were calculated. For each bridging segment, the presence of atherosclerosis was saved in a 2-cm-long segment proximal to the entry of the bridging segment. The degree of stenosis made by atherosclerotic plaques was determined.ResultsLAD myocardial bridging was detected in 410 (10.4%) patients. Among these, 97 (23.7%) patients had a deep and 313 (76.3%) patients had a superficial course. The mean LAD MB length was 20.28 ±9.63 mm and the depth was 1.72 ±1.11 mm. The systolic and diastolic mean diameter difference was 0.193 mm and the average compression ratio was 9.44%. Atherosclerotic plaques were found in 167 (40.7%) of 410 LAD MB. Atherosclerotic plaques were found in 50.5% of deep MB and 37.7% of superficial MB.Conclusions256-slice MDCT coronary angiography has a high sensitivity to show myocardial bridging in LAD localization, to determine length, depth, compression ratio, atherosclerotic plaque localization and degree of stenosis.

Study of the Relationship Between Mean Platelet Volume and LAD as a Culprit Vessel in NSTEMI

Background: Among acute coronary patients, the ratio of non ST-elevation myocardial infarction (NSTEMI) is increasing and according to recent studies, less than 30% of myocardial infarctions (MIs) are due to ST-elevation myocardial infarction (STEMI). Unlike STEMI, in NSTEMI the ECG is not able to identify the culprit vessel. Objectives: In this study, we aimed to evaluate the association of mean platelet volume (MPV) and NSTEMI due to left anterior descending lesion. Methods: In this cross sectional study 349 patients with NSTEMI were included. Major cardiac risk factors (cigarette, diabetes mellitus (DM), hypertension (HTN), hyperlipidemia (HLP), angiographic findings, and drug history of patients were extracted from patients’ medical files. Then the MPV in complete blood count results and angiography findings were analyzed for any association. According to culprit lesions patients were divided into left anterior descending (LAD) and non-LAD groups. Results: There was a significant difference between the two groups (LAD vs. non-LAD) according to platelet count (P = 0.014), MPV (P = 0.001), HLP (0.024) and DM (0.048). Multivariate regression model has shown the MPV (OR = 0.46, 95%CI = 0.27 - 0.78) and DM (OR = 0.18, 95%CI = 0.06 - 0.54) as independent risk factors for NSTEMI due to LAD lesion. The significant positive correlation was also seen between MPV and left ventricle ejection fraction (LVEF) (r = 0.22, P = 0.006). The area under the curve (AUC) of MPV for predicting LAD culprit lesion was calculated as 69% (P &lt; 0.0001). At cut off point of 9.15, has sensitivity and specificity of MPV for predicting LAD as culprit vessel was 100% and 30% respectively. Conclusions: In NSTEMI patients MPV might be a good tool to differentiate patients with LAD as culprit vessel.

Value of Two-Dimensional Strain Imaging in Prediction of Myocardial Function Recovery After Percutaneous Revascularization of Infarct-Related Artery

Background: Acute myocardial infarction (MI) is often accompanied by impaired regional myocardial systolic function. A novel approach known as two-dimensional speckle tracking echocardiography was used to quantify regional LV function. Objective: The aim of the current study was to evaluate of the role of Speckle Tracking Echocardiography in prediction of left ventricular function recovery after percutaneous coronary intervention to left anterior descending coronary artery in patients with anterior ST segment elevation myocardial infarction with impaired left ventricular ejection fraction. Patients and methods: This study included 50 patients and 15 normal control adult persons. Patients had suffered from first attack of anterior STEMI. They were admitted at the CCU units of Al-Azhar University Hospitals from September 2016 to September 2018 and treated with thrombolytic therapy. Each patient was subjected to conventional transthoracic echocardiography before hospital discharge and before reperfusion. Speckle tracking echocardiography and resting SPECT were done one week after MI. Percutaneous coronary intervention to LAD within one week after MI for patients with demonstrated myocardial viability by resting SPECT. Three months after percutaneous revascularization to LAD, all patients were reevaluated using conventional TTE and strain imaging. The studied population were divided into 2 Groups; group A: 24 patients who showed post-PCI LV function recovery and Group B: 26 patients who did not showed post-PCI LV function recovery. Results: There was statistically significant increase in the prevalence of diabetes mellitus, smoking and dyslipidemia in group B. There was high statistically significant difference between the two groups as regard baseline LVEF (%), baseline wall motion score index (WMSI), mean baseline and follow up WMSI values, baseline number of affected left anterior descending (LAD) segments as assessed by WMSI, baseline and 90 days follow up mean number of affected LAD segments, baseline strain values at both global LV and territorial LAD segments. Control group showed mean territorial LAD strain was - 20.41± 0.61, mean baseline territorial LAD strain of group (A) - 13.20 ± 2.05 and mean baseline territorial LAD strain of group (B) - 8.47 ± 2.12. Regarding mean baseline territorial LAD strain and mean GLS of the LV, Receiver Operating Characteristic curve was done between group A and B for obtaining a cut off value of – 11.3 % and – 11.8 % respectively. Conclusion: LV global and territorial strain measured by 2D STE is a good predictor of LV function recovery in STEMI patients after percutaneous revascularization of infarct–related artery.

Comparative treatment planning study for mediastinal Hodgkin’s lymphoma: impact on normal tissue dose using deep inspiration breath hold proton and photon therapy

Background: Late effects induced by radiotherapy (RT) are of great concern for mediastinal Hodgkin’s lymphoma (HL) patients and it is therefore important to reduce normal tissue dose. The aim of this study was to investigate the impact on the normal tissue dose and target coverage, using various combinations of intensity modulated proton therapy (IMPT), volumetric modulated arc therapy (VMAT) and 3-dimensional conformal RT (3D-CRT), planned in both deep inspiration breath hold (DIBH) and free breathing (FB).Material and methods: Eighteen patients were enrolled in this study and planned with involved site RT. Two computed tomography images were acquired for each patient, one during DIBH and one during FB. Six treatment plans were created for each patient; 3D-CRT in FB, 3D-CRT in DIBH, VMAT in FB, VMAT in DIBH, IMPT in FB and IMPT in DIBH. Dosimetric impact on the heart, left anterior descending (LAD) coronary artery, lungs, female breasts, target coverage, and also conformity index and integral dose (ID), was compared between the different treatment techniques.Results: The use of DIBH significantly reduced the lung dose for all three treatment techniques, however, no significant difference in the dose to the female breasts was observed. Regarding the heart and LAD doses, large individual variations were observed. For VMAT, the mean heart and LAD doses were significantly reduced using DIBH, but no significant difference was observed for 3D-CRT and IMPT. Both IMPT and VMAT resulted in improved target coverage and more conform dose distributions compared to 3D-CRT. IMPT generally showed the lowest organs at risk (OAR) doses and significantly reduced the ID compared to both 3D-CRT and VMAT.Conclusions: The majority of patients benefited from treatment in DIBH, however, the impact on the normal tissue dose was highly individual and therefore comparative treatment planning is encouraged. The lowest OAR doses were generally observed for IMPT in combination with DIBH.

Spatial orientation of coronary arteries and its implication for breast and thoracic radiotherapy-proposing "coronary strip" as anew organ at risk.

Radiotherapy for breast cancer has been associated with various side effects including cardiac sequelae. Our study aimed to define the spatial arc of spread of coronary vessels in aradian angle. We analysed the records of 51CT coronary angiographies done in our hospital from January 2016 to July 2016. Left anterior descending (LAD) and right coronary (RC) were contoured for each patient. In each axial section, the radial spread of each artery was noted. A5 mm brush tool was used to join the start and stop angles for making the summated "coronary strips". Start and end angle of LAD with 95% confidence interval (CI) (in clockwise direction) were 23.9 ± 4° and 79.0 ± 6.6°, respectively. Mean LAD arc length ± SD (standard deviation) noted was 55.1° ± 7.7° (95% CI). For RC the smallest start angle and the largest end angle in all patients was 297.6° and 322.6°, respectively. RC start angle, end angle and arc length for 95% confidence interval were 322.2 ± 6.1°, 292.4 ± 11.6° and 29.8 ± 13.1°, respectively. Our study provides ameasure of the radial spread of the coronary arteries, especially from the perspective of breast radiotherapy. We have proposed anew organ at risk (OAR) of coronary strip. This should provide an easy and cost-effective way to delineate the coronary vasculature in breast cancer patients undergoing radiotherapy.

Does mean heart dose sufficiently reflect coronary artery exposure in left-sided breast cancer radiotherapy? : Influence of respiratory gating.

With extensive use of systemic treatment, the issue of cardiac mortality after breast cancer radiation (RT) is still important. The aim of our analysis was to clarify whether the dose to one surrogate parameter (e. g., mean heart dose, as used in most studies) reflects the dose to the other cardiovascular structures especially the left anterior descending artery depending on breathing-adapted RT. Atotal of 130 patients who underwent adjuvant RT (50.4Gy plus boost 9-16Gy) were evaluated. In all, 71patients were treated with free-breathing and 59patients using respiratory monitoring (gated RT). Dosimetric associations were calculated. The mean dose to the heart (Dmean heart) was reduced from 2.7 (0.8-5.2) Gy to 2.4 (1.1-4.6) Gy, the Dmean LAD (left anterior descending artery) decreased from 11.1 (1.3-28.6) Gy to 9.3 (2.2-19.9) Gy with gated RT (p= 0.04). Asignificant relationship was shown for Dmean heart-Dmean LAD, V25heart-Dmean LAD and Dmax heart-Dmax LAD for gated patients only (p< 0.01). For every 1Gy increase in Dmean heart, mean LAD doses rose by 3.6Gy, without gating V25 ≤5 % did not assure abenefit and resulted in Dmean LAD between 1.3 and 28.6Gy. Asignificant reduction and association of heart and coronary artery (LAD) doses using inspiratory gating was shown. However, in free-breathing plans commonly measured dose constraints do not allow precise estimation of the dose to the coronary arteries.

Monitoring ABC-assisted deep inspiration breath hold for left-sided breast radiotherapy with an optical tracking system.

Recent knowledge on the effects of cardiac toxicity warrants greater precision for left-sided breast radiotherapy. Different breath-hold (BH) maneuvers (abdominal vs thoracic breathing) can lead to chest wall positional variations, even though the patient's tidal volume remains consistent. This study aims to investigate the feasibility of using optical tracking for real-time quality control of active breathing coordinator (ABC)-assisted deep inspiration BH (DIBH). An in-house optical tracking system (OTS) was used to monitor ABC-assisted DIBH. The stability and localization accuracy of the OTS were assessed with a ball-bearing phantom. Seven patients with left-sided breast cancer were included. A free-breathing (FB) computed tomography (CT) scan and an ABC-assisted BH CT scan were acquired for each patient. The OTS tracked an infrared (IR) marker affixed over the patient's xiphoid process to measure the positional variation of each individual BH. Using the BH within which the CT scan was performed as the reference, the authors quantified intra- and interfraction BH variations for each patient. To estimate the dosimetric impact of BH variations, the authors studied the positional correlation between the marker and the left breast using the FB CT and BH CT scans. The positional variations of 860 BHs as measured by the OTS were retrospectively incorporated into the original treatment plans to evaluate their dosimetric impact on breast and cardiac organs [heart and left anterior descending (LAD) artery]. The stability and localization accuracy of the OTS was within 0.2 mm along each direction. The mean intrafraction variation among treatment BHs was less than 2.8 mm in all directions. Up to 12.6 mm anteroposterior undershoot, where the patient's chest wall displacement of a BH is less than that of a reference BH, was observed with averages of 4.4, 3.6, and 0.1 mm in the anteroposterior, craniocaudal, and mediolateral directions, respectively. A high positional correlation between the marker and the breast was found in the anteroposterior and craniocaudal directions with respective Pearson correlation values of 0.95 and 0.93, but no mediolateral correlation was found. Dosimetric impact of BH variations on breast coverage was negligible. However, the mean heart dose, mean LAD dose, and max LAD dose were estimated to increase from 1.4/7.4/18.6 Gy (planned) to 2.1/15.7/31.0 Gy (delivered), respectively. In ABC-assisted DIBH, large positional variation can occur in some patients, due to their different BH maneuvers. The authors' study has shown that OTS can be a valuable tool for real-time quality control of ABC-assisted DIBH.

Analysis of coronary artery dosimetry in the 3-dimensional era: Implications for organ-at-risk segmentation and dose tolerances in left-sided tangential breast radiation

PurposeTo evaluate the dose to the left anterior descending artery in patients receiving left-sided tangential breast radiation. Methods and MaterialsThe study cohort consisted of 50 left-sided breast cancer patients who were sequentially simulated at our institution. The heart and left anterior descending (LAD) artery were contoured from its origin on the left main coronary artery down to the last visible segment of the vessel. Detailed dosimetry of the heart and LAD artery were obtained and analyzed. ResultsExcellent correlation between the dose to the heart and LAD artery was discovered. The mean LAD dose was 17.98 Gy. The mean dose to the proximal LAD was 2.46 Gy. The median V25 was 2.91% and the mean heart dose 3.10 Gy. For every 100 cGy increase in mean heart dose, mean LAD dose increased by 4.82 Gy. For every percent increase in the heart V10 and V25, there was a 2.23 Gy and 2.77 Gy increase in mean LAD dose, respectively. For every percent increase of heart V25, a 5.6% increase in the LAD V20 was demonstrated. ConclusionsThe LAD artery dose correlates very closely with all of the commonly measured heart dose constraints, and does not need to be contoured separately when standard tangential borders are used. Incidental LAD artery doses remain with supine breast tangential radiation therapy.

Quantifying the Reproducibility of Heart Position During Treatment and Corresponding Delivered Heart Dose in Voluntary Deep Inhalation Breath Hold for Left Breast Cancer Patients Treated With External Beam Radiotherapy

Voluntary deep inhalation breath hold (VDIBH) reduces heart dose during left breast irradiation. We present results of the first study performed to quantify reproducibility of breath hold using bony anatomy, heart position, and heart dose for VDIBH patients at treatment table. Data from 10 left breast cancer patients undergoing VDIBH whole-breast irradiation were analyzed. Two computed tomography (CT) scans, free breathing (FB) and VDIBH, were acquired to compare dose to critical structures. Pretreatment weekly kV orthogonal images and tangential ports were acquired. The displacement difference from spinal cord to sternum across the isocenter between coregistered planning Digitally Reconstructed Radiographs (DRRs) and kV imaging of bony thorax is a measure of breath hold reproducibility. The difference between bony coregistration and heart coregistration was the measured heart shift if the patient is aligned to bony anatomy. Percentage of dose reductions from FB to VDIBH: mean heart dose (48%, SD 19%, p = 0.002), mean LAD dose (43%, SD 19%, p = 0.008), and maximum left anterior descending (LAD) dose (60%, SD 22%, p = 0.008). Average breath hold reproducibility using bony anatomy across the isocenter along the anteroposterior (AP) plane from planning to treatment is 1 (range, 0-3; SD, 1) mm. Average heart shifts with respect to bony anatomy between different breath holds are 2 ± 3 mm inferior, 1 ± 2 mm right, and 1 ± 3 mm posterior. Percentage dose changes from planning to delivery: mean heart dose (7%, SD 6%); mean LAD dose, ((9%, SD 7%)S, and maximum LAD dose, (11%, SD 11%) SD 11%, p = 0.008). We observed excellent three-dimensional bony registration between planning and pretreatment imaging. Reduced delivered dose to heart and LAD is maintained throughout VDIBH treatment.

Estimating Cardiac Exposure From Breast Cancer Radiotherapy in Clinical Practice

To assess the value of maximum heart distance (MHD) in predicting the dose and biologically effective dose (BED) to the heart and the left anterior descending (LAD) coronary artery for left-tangential breast or chest wall irradiation. A total of 50 consecutive breast cancer patients given adjuvant left-tangential irradiation at a large U.K. radiotherapy center during 2006 were selected. For each patient, the following were derived using three-dimensional computed tomography (CT) planning: (1) mean dose and BED to the heart, (2) mean dose and BED to the LAD coronary artery, (3) MHD, (4) position of the CT slice showing the maximum area of the irradiated heart relative to the mid-plane slice, and (5) sternal and contralateral breast thickness (measures of body fat). A strong linear correlation was found between the MHD and the mean heart dose. For every 1-cm increase in MHD, the mean heart dose increased by 2.9% on average (95% confidence interval 2.5-3.3). A strong linear-quadratic relationship was seen between the MHD and the mean heart BED. The mean LAD coronary artery dose and BED were also correlated with the MHD but the associations were weaker. These relationships were not affected by body fat. The mid-plane CT slice did not give a reliable assessment of cardiac irradiation. The MHD is a reliable predictor of the mean heart dose and BED and gives an approximate estimate of the mean LAD coronary artery dose and BED. Doses predicted by the MHD could help assess the risk of radiation-induced cardiac toxicity where individual CT-based cardiac dosimetry is not possible.

Intra‐aortic Balloon Pumping: Does Posture Matter?

The effect of the posture of semirecumbent patients on the hemodynamics and performance of intra-aortic balloon (IAB) were studied in vivo and in vitro. An IAB was inserted into a glass tube filled with saline, fully inflated and deflated using an intra-aortic balloon pump (IABP). Three successive cycles were filmed at 125 frames/s with the tube positioned at various angles between 0 degrees (horizontal) and 90 degrees (vertical). Pressure and flow were measured distal to both ends of the balloon. In parallel, coronary left anterior descending (LAD) flow velocity and aortic pressure were recorded in 6 patients using IABP, postcardiac surgery in the intensive care unit. Recordings were made when the patient was lying horizontally (recumbent) and when the patient's torso was inclined at 30 degrees to the horizontal (semirecumbent). With the tube horizontal, the inflation was effectively uniform along the length of the balloon. At all other angles, the higher end of the balloon inflated first, and mean pressure and flow measured distal to the higher end of the balloon were less than those measured at 0 degrees . Mean aortic pressure and LAD flow decreased by 10 +/- 2% (P = 0.001) and 15 +/- 3% (P = 0.001), respectively, when the patient was semirecumbent compared to when the patient was recumbent. The decreased mean aortic pressure and LAD flow velocity suggests that unless patients using IABP are required to be semirecumbent, it may be best to position them horizontally to gain the full benefits of balloon counter pulsation to the coronary circulation.

Sex differences in coronary artery size assessed by intravascular ultrasound

Background Women have worse outcomes after myocardial infarction and coronary revascularization. The explanations are likely multifactorial but may include smaller coronary artery size. Smaller luminal diameter has been confirmed angiographically; however, because of possible confounding effects of coronary remodeling, angiographically silent atherosclerosis, and body size, it is unclear if there is a true sex influence on arterial size. Methods We performed intravascular ultrasound on left main (LM) and proximal left anterior descending (LAD) coronary artery segments that were free of significant atherosclerosis in 50 men and 25 women. Arterial and luminal areas were measured by planimetry and corrected for body surface area. We evaluated associations between sex and coronary dimensions with univariate and then multiple linear regression analyses. Results Mean uncorrected LM and LAD arterial areas were smaller in women than in men (21.53 vs 26.95 mm 2, P < .001, and 14.68 vs 19.94 mm 2, P = .002, respectively), as were mean LM and LAD luminal areas (15.94 vs 18.79 mm 2, P = .020, and 10.13 vs 12.71 mm 2, P = .036, respectively). In multivariate models accounting for body surface area and controlling for other factors, sex independently predicted corrected LM and LAD arterial area. In analyses that additionally controlled for plaque area, sex independently predicted corrected LAD luminal area. Conclusions LM and LAD arteries are smaller in women, independent of body size. This suggests an intrinsic sex effect on coronary dimensions. Future studies should investigate underlying mechanisms because they may lead to novel therapeutic strategies and improved outcomes for women with coronary artery disease.

Systolic rightward displacement of the left anterior descending artery: a novel cineangiographic sign for tricuspid regurgitation.

A new sign for the detection of tricuspid regurgitation (TR) is described. The systolic displacement of the left anterior descending (LAD) artery during coronary angiography in left anterior oblique (LAO) view was quantitatively calculated in 3 groups of 20 patients each with either TR, mitral stenosis, or normal coronary arteriograms. The mean LAD displacement in the TR group was significantly rightward compared to the other groups. Uniform rightward displacement of the lower two-thirds of the LAD had a 90% sensitivity and 90-95% specificity for the presence of TR. Such displacement is probably the angiographic counterpart of the systolic paradoxical septal displacement demonstrated by echocardiography in patients with right ventricular volume overload. There was a positive correlation between the severity of TR and the magnitude of LAD displacement. Attention to the LAD displacement on LAO view may raise suspicion of TR, and indicate its severity.