Model-based comparison of organ at risk protection between VMAT and robustly optimised IMPT plans.

The comparison between intensity-modulated proton therapy (IMPT) and volume-modulated arc therapy (VMAT) plans, based on models of normal tissue complication probabilities (NTCP), can support the choice of radiation modality. IMPT irradiation plans for 50 patients with head and neck tumours originally treated with photon therapy have been robustly optimised against density and setup uncertainties. The dose distribution has been calculated with a Monte Carlo (MC) algorithm. The comparison of the plans was based on dose-volume parameters in organs at risk (OARs) and NTCP-calculations for xerostomia, sticky saliva, dysphagia and tube feeding using Langendijk's model-based approach. While the dose distribution in the target volumes is similar, the IMPT plans show better protection of OARs. Therefore, it is not the high dose confirmation that constitutes the advantage of protons, but it is the reduction of the mid-to-low dose levels compared to photons. This work investigates to what extent the advantages of proton radiation are beneficial for the patient's post-therapeutic quality of life (QoL). As a result, approximately one third of the patients examined benefit significantly from proton therapy with regard to possible late side effects. Clinical data is needed to confirm the model-based calculations.

Proton Therapy for Craniopharyngioma - An Early Report from a Single European Centre.

AIMS: Proton beam therapy (PBT) is being increasingly used for craniopharyngioma. We describe our early outcome of patients treated with PBT. MATERIALS AND METHODS: Between August 2013 and July 2016, 18 patients with craniopharyngiomas were treated with 54 Cobalt Gray Equivalent (CGE) in 30 fractions over 6 weeks at our centre. The early outcome of 16 patients included in a registry study was analysed. Radiological response was assessed by RECIST criteria and the disease- and treatment-related toxicities were scored according to the CTCAE 4.0. RESULTS: All patients are alive at a median follow-up of 32.6 months (range 9.2-70.6 months) from initial diagnosis. The median age at PBT was 10.2 years (range 5.4-46.9 years). One patient progressed 8.7 months after PBT and subsequently had complete resection of the tumour. At a median follow-up of 18.4 months after PBT, five patients remained in complete remission, four in partial remission and seven with stable disease. The most common adverse effects during PBT were grade 1 (cutaneous in seven patients and fatigue in six patients). There were no treatment-related grade 3 toxicities. CONCLUSIONS: Our early results are encouraging and comparable with the limited literature on PBT for craniopharyngioma.

Comprehensive clinical commissioning and validation of the RayStation treatment planning system for proton therapy with active scanning and passive treatment techniques.

PURPOSE: To commission the treatment planning system (TPS) RayStation for proton therapy including beam models for spot scanning and for uniform scanning. METHODS: Tests consist of procedures from ESTRO booklet number 7, the German DIN for constancy checks of TPSs, and extra tests checking the dose perturbation function. The dose distributions within patients were verified in silico by a comparison of 65 clinical treatment plans with the TPS XiO. Dose-volume parameters, dose differences, and three-dimensional gamma-indices serve as measures of similarity. The monthly constancy checks of Raystation have been automatized with a script. RESULTS: The basic functionality of the software complies with ESTRO booklet number 7. For a few features minor enhancements are suggested. The dose distribution in RayStation agrees with the calculation in XiO. This is supported by a gamma-index (3mm/3%) pass rate of >98.9% (median over 59 plans) for the volume within the 20% isodose line and a difference of <0.3% of V95 of the PTV (median over 59 plans). If spot scanning is used together with a range shifter, the dose level calculated by RayStation can be off by a few percent. CONCLUSIONS: RayStation can be used for the creation of clinical proton treatment plans. Compared to XiO RayStation has an improved modelling of the lateral dose fall-off in passively delivered fields. For spot scanning fields with range shifter blocks an empirical adjustment of monitor units is required. The computation of perturbed doses also allows the evaluation of the robustness of a treatment plan.

Stress echocardiography: technical considerations.

Stress echocardiography has evolved into a widely practiced and accepted method for the noninvasive assessment of the status of the coronary anatomy. Furthermore, this modality incorporates the ability to assess left ventricular function, valvular structure and function, intracardiac masses, the pericardium, and hemodynamics. The extent to which this tool can reliably provide useful clinical information is dependent, in part, on optimal performance. The purpose of this report is to provide an overview of those technical considerations that can contribute to the successful operation of a stress echocardiography laboratory. Consideration is given to personnel qualifications, functional requirements of the digital acquisition/storage/replay system, functional integration of the various hardware components, characteristics of the software, physical layout of the facility, and alternatives to treadmill exercise as the stressor. A thorough understanding of the physiologic basis of stress echocardiography, coupled with optimization of resources used in its performance, enable this tool to be an extraordinarily useful and cost-efficient method for comprehensive cardiovascular assessment.

Use of exercise echocardiography to evaluate patients after coronary angioplasty.

Exercise echocardiography is a sensitive, specific, and highly accurate method for detecting coronary restenosis and progressive compromise of untreated arterial segments in patients who have undergone percutaneous transluminal coronary angioplasty. It is far more reliable in predicting the status of the coronary anatomy in such patients than exercise electrocardiography or symptomatic status.

Are there gender differences related to stress or pharmacological echocardiography?

Coronary artery disease (CAD) is the leading cause of adult mortality in the United States. Data collected from the era preceding contemporary revascularization techniques indicated that chest pain syndromes among women carried a more favorable cardiac prognosis than such symptoms in men. More recent information indicates that many women with chest pain do not have CAD and that, among those who do, clinical manifestations first appear an average of 10 years later than in men, at a time when risk factors and comorbidities such as diabetes, hypertension, and hypercholesterolemia are more prevalent. The toll that this disease exacts among women catches up with that among men after women go through menopause, so that coronary heart disease accounts for nearly equal annual mortality rates in the two genders and for more deaths among women than is attributable to all cancers. The initial, widely held impression that chest pain is more benign in women is being replaced by a growing awareness that coronary disease is not. It appears from published experience that any potential bias in the management of women with possible CAD is overcome once the diagnosis is established. It is clear that a reliable method for the evaluation of women with known or suspected CAD is required. Stress electrocardiography, perfusion imaging, and radioventriculography suffer from a number of limitations, particularly in women. This paper discusses the rationale for and performance of stress echocardiography. Although the specific application of this method in females has been the subject of relatively limited clinical investigations, we believe that it holds great promise as the diagnostic test of choice for women.

Comparison of results of coronary angioplasty during acute myocardial infarction with and without previous coronary bypass surgery.

Six hundred one consecutive patients undergoing reperfusion within 6 hours of acute myocardial infarction were studied with regard to impact of previous coronary artery bypass grafting (CABG) on direct coronary angioplasty performance and results. Forty-nine patients (8%) had previously undergone CABG, whereas 552 (92%) had not. Direct angioplasty was used for reperfusion in 35 patients (71%) in the CABG group, and in 258 (47%) in the non-CABG group (p < 0.01). No significant differences between these groups were noted with regard to gender, age, infarction site, time to reperfusion or angioplasty success (34 of 35 CABG patients [97%] vs 236 of 258 non-CABG patients [92%]). CABG patients were more likely to have had previous infarction (17 of 35 [49%] vs 35 of 258 [14%] [p < 0.001]), multivessel disease (34 of 35 [97%] vs 127 of 258 [49%] [p < 0.001]) and lower mean ejection fraction (0.36 +/- 0.13 vs 0.46 +/- 0.12, p < 0.001). Over a mean follow-up of 151 weeks, 24 patients (69%) in the CABG group were restudied versus 112 (43%) in the non-CABG group (p < 0.01). Restenosis occurred in 14 patients (40%) in the CABG group versus 58 (22%) in the group without previous CABG (p = 0.04). In the CABG group, restenosis occurred significantly more often in saphenous vein grafts than in native vessels (12 of 17 [71%] vs 2 of 11 [18%] [p < 0.02]). There was no significant difference in the overall performance of repeat angioplasty between the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Sex-related differences in patients undergoing direct angioplasty for acute myocardial infarction.

Important sex-related differences have been recognized in several coronary artery disease presentation and treatment subsets. Little data exist describing the relative findings and outcome in women versus men who received direct percutaneous transluminal coronary angioplasty for acute myocardial infarction. We studied 670 such patients of whom 464 (69%) were men and 206 were women. The women were significantly older (67 +/- 11 years vs 61 +/- 11, p < 0.001) but had undergone less prior coronary artery bypass graft surgery (6% vs 12%, p = 0.02), whereas prior myocardial infarction (17% women vs 22% men) and coronary artery disease distribution were not significantly different. Forty-one percent of women and 43% of men had single-vessel disease (p = NS). Both women and men had 1.5 lesions/patient dilated acutely, with similar success rates (95% women, 91% men; p = 0.08). Mean ejection fractions were similar (48% in both groups), and a similar percentage in each group had an ejection fraction < 30% (10% women vs 13% men). Over a mean follow-up period of 86 weeks, the need for repeat catheterization was frequent and was similar in both groups (44% women, 47% men; p = NS), whereas documented restenosis was less common in women (20% vs 28% of patients, p < 0.05). The need for coronary artery bypass grafting was similar (15% women, 17% men; p = NS), as was the need for repeat percutaneous transluminal coronary angioplasty in the infarct vessel (14% women, 18% men; p = NS) and overall mortality (7% women, 9% men; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Direct angioplasty versus initial thrombolytic therapy for acute myocardial infarction: long-term follow-up and changes in practice pattern.

We retrospectively studied the outcomes of patients with acute myocardial infarction who were treated with either direct angioplasty or thrombolytics followed by angioplasty. Two patient cohorts were analyzed: a previously reported (in regard to short-term follow-up) group of 371 patients who now have long-term follow-up (mean, 3.4 years) of survival and event-free survival and a second group of 202 patients who have been treated since publication of our initial data. Both 1-year and 2-year survival were significantly better (p = 0.01 and 0.02, respectively) in the group that was treated with thrombolytics first. Event-free survival (i.e., no myocardial infarction, coronary artery bypass graft surgery, repeat angioplasty) was better overall (p < 0.01) for the group that was treated with thrombolytics first. The more recently treated group of patients also showed benefit in regard to both survival (p = 0.002) and event-free survival (p < 0.01) over a short-term follow-up period (mean, 39 weeks) for patients who were treated initially with thrombolytics as compared with those who were treated with direct angioplasty. Although the initial cohort was very similar to the treatment groups except for age (mean age for the direct angioplasty group was 62 +/- 12 years vs 57 +/- 11 years for thrombolytics first group, (p = 0.0002), several differences existed in the more recent treatment groups. The patients who were more recently treated with direct angioplasty were older, had lower mean ejection fraction, had more extensive coronary artery disease, and were more likely to have had prior coronary artery bypass grafting.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise echocardiography after coronary artery bypass grafting.

Exercise echocardiography was used to assess the adequacy of regional myocardial perfusion in 125 patients who had undergone coronary artery bypass grafting. There were 108 men and 17 women (mean age 65 years) evaluated from 6 weeks to 16 years (mean 7 years) after surgery. Resting parasternal long- and short-axis and apical 4- and 2-chamber echocardiograms were recorded, digitized and stored. Maximal, symptom-limited upright treadmill exercise was then performed with continuous electrocardiographic monitoring. Repeat echocardiographic imaging and digitization were repeated within 1 minute of exercise termination. Resting and postexercise digitized echocardiograms were compared. A normal regional wall motion response to exercise consisted of improved segmental contraction and was used to predict uncompromised regional vascular supply. Unimproved or worsened segmental contraction after exercise was abnormal and was used as a predictor of regional vascular insufficiency. All patients underwent cardiac catheterization within 1 month after exercise testing. Regional coronary insufficiency was considered to exist when a segment's major vascular conduit exhibited greater than or equal to 50% luminal diameter reduction. Compared with the simultaneously acquired stress electrocardiogram, exercise echocardiography had superior sensitivity (98 vs 41%), specificity (92 vs 67%), positive predictive value (99 vs 91%), and negative predictive value (86 vs 12%) (p less than 0.001, 0.1, 0.01 and less than 0.001, respectively). In addition, exercise echocardiography correlated closely with the extent and regional distribution of compromised vascular supply. Exercise echocardiography is a highly sensitive, specific and accurate screening test for abnormal global and regional myocardial vascular supply in patients who have undergone coronary artery bypass grafting.

Anticoagulant effect of iohexol vs. ioxaglate during cardiac catheterization.

Contrast agent safety during cardiac catheterization (CC) may relate in part to anti- or procoagulant effect. We studied these effects in 177 patients who underwent standard CC (N=112) or percutaneous transluminal coronary angioplasty (PTCA) (N=65) and received either iohexol (N=111) or ioxaglate (N=66). Patients received either 0 or 2000u heparin for CC or 10,000u for PTCA. The groups were similar in regards to age, sex, amount of contrast used, and procedure time. Partial thromboplastin time (PTT) and activated clotting time (ACT) were both significantly increased (P less than .01) in patients who received 10,000u heparin irrespective of type of contrast agent although larger increases were seen in the iohexol group. With 2000u of heparin, ACT and PTT increased significantly (P less than .01) only in the iohexol group. PTT and ACT actually decreased to similar and significant (P less than .01) degrees after both iohexol and ioxaglate when heparin was not used. We conclude: 1) commonly used measures of anticoagulant (ACT and PTT) show greater prolongation after either 2000 or 10,000u of heparin with iohexol than ioxaglate, 2) ACT and PCT appear to shorten with both iohexol and ioxaglate if no heparin is used. This data would suggest that ioxaglate does not have an anticoagulant advantage over iohexol.

Clinical applicability of echocardiographically detected regional wall-motion abnormalities provoked by upright treadmill exercise.

Exercise electrocardiography is the time-honored screening test for coronary artery disease but has serious limitations in many patient subgroups. A number of adjunctive modalities have been coupled to exercise ECG to increase the diagnostic accuracy of noninvasive testing, including thallium scintigraphy and gated blood pool radioventriculography. Exercise echocardiography has more recently emerged as a tool that can detect exercise-induced regional wall-motion abnormalities as an indicator of provoked myocardial ischemia. While there are conceptual advantages to performing echocardiography during maximal exercise, we have found that regional wall-motion analysis performed with echocardiograms obtained before and immediately after upright treadmill exercise allows highly accurate prediction of the extent and distribution of coronary artery disease as detected by angiography. This monograph summarizes our experience with this form of exercise echocardiography in three important patient groups: (1) patients being screened for the presence or absence of coronary artery disease; (2) patients who have undergone previous coronary artery bypass surgery and who are being evaluated for graft failure and/or progression of native-vessel disease; and (3) patients who have undergone coronary angioplasty and are at risk for restenosis and/or progression of disease. We believe, based on our experience and that of other investigators, that exercise echocardiography is a uniquely valuable tool in these and other patients for assessing the status of the coronary vascular anatomy. Not only can the presence or absence of obstructive disease be assessed, but the extent and distribution of disease can be accurately predicted, and other, noncoronary causes of chest pain such as aortic stenosis, mitral valve prolapse, hypertrophic cardiomyopathy, and pericardial disease can readily be identified.

Prognosis of culprit lesion PTCA in acute myocardial infarction for multi versus single vessel disease.

UNLABELLED: We studied 417 patients undergoing single vessel culprit lesion percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction to determine the impact of disease in other vessels. Group A (189 patients, 45%) had coronary artery disease (greater than or equal to 70% stenosis) in at least 1 additional vessel while Group B (228 patients, 55%) did not. The groups were similar in sex distribution (A = 75% male, B = 76%), number of lesions in the single culprit vessel dilated (1 lesion in 83% A, 80% B), and PTCA success (A = 92%, B-94%) (all p = NS). Group A patients were older (63 +/- 10 vs. 56 +/- 11 years) and had more prior myocardial infarctions (27% vs. 7%), and more prior coronary artery bypass grafting (15% vs. 0.4%) (all p less than .01). Group A patients were more likely to have repeat catheterization (48% vs. 32%, p less than .005) although restenosis of the infarct-related vessel was similar (A = 24%, B = 16%) (p = NS). Group A was more likely to need angioplasty in a 2nd vessel (23% vs. 8%) and to need coronary artery bypass grafting (20% vs. 8%) (both p less than .001). Cumulative mortality was higher in Group A at 1 month (10% vs. 5%), 1 year (11% vs. 6%), and long-term (13% vs. 7%). This difference appeared to be due to the impact of lower mean ejection fraction in Group A. CONCLUSION: Treatment of acute myocardial infarction by direct PTCA of the culprit lesion can be performed with a high likelihood of success in patients with or without multivessel coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Opacification and border delineation improvement in patients with suboptimal endocardial border definition on routine echocardiography: results of a phase III trial of sonicated albumin microspheres.

To determine whether contrast medium in the left ventricle improves endocardial border delineation, enabling better assessment of left ventricular (LV) wall motion, a 5% solution of sonicated albumin microspheres was administered in 30 adult patients who exhibited endocardial border drop-out of 20% or more on routine echocardiography. The investigator and two blinded reviewers evaluated efficacy using an opacification grading system of 0 to 3+, with 0 indicating no contrast effect and 3+ indicating full opacification of the left ventricle. A score of 2+ or greater indicated effective opacification. Border delineation improvement was defined as a change from grade A (not well delineated) to grade B, C, or D (well delineated) of at least 1 of 6 LV wall segments. All patients received an initial injection of 0.08 cc/kg. If this volume produced LV opacification of at least 2+, the patient received two additional injections of 0.14 cc/kg and 0.08 cc/kg, each given 5 minutes apart. Otherwise, the patient received a final injection of 0.22 cc/kg. In all cases, the patient's arm was raised after injection to enhance venous passage. The total number of patients exhibiting 2+ or greater opacification was 29 (97%) when graded by the investigator and 27 (90%) when graded by the blinded observers. The investigator noted improved border delineation in 90% of patients, and the blinded observers noted improvement in 97% (excluding 1 patient who would have received a higher dose of contrast agents if scored by a blinded observer). Investigator confidence in assessing LV wall motion improved in 24 (80%) of the 30 studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise echocardiography as a screening test for coronary artery disease and correlation with coronary arteriography.

We evaluated exercise echocardiography as a screening test for coronary artery disease in 228 patients, all of whom underwent subsequent coronary angiography. After an echocardiogram at rest was obtained, each patient performed maximal, symptom-limited, upright treadmill exercise, immediately after which repeat imaging was performed. The exercise echocardiogram was abnormal if any segment failed to become hypercontractile with exercise, and these regional wall motion abnormalities were used to predict the extent and distribution of coronary disease. At subsequent angiography, coronary stenosis was defined as significant if luminal diameter was reduced greater than or equal to 50%. Compared with electrocardiography, exercise echocardiography was more sensitive (97 vs 51%) and specific (64 vs 62%), and had higher positive (90 vs 82%) and negative (87 vs 28%) predictive accuracies. Exercise echocardiography was also highly predictive of the extent (no, 1-, 2- or 3-vessel disease) and distribution (which vessel) of coronary stenoses. It is concluded that exercise echocardiography is an excellent screening test for the presence, extent and distribution of coronary artery disease.

Exercise echocardiography follow-up in percutaneous transluminal coronary angioplasty.

Exercise echocardiography has emerged as an excellent tool in the diagnosis of coronary artery disease and has proven to correlate very closely with the distribution and extent of coronary stenoses. In this report we describe our experience with the use of this noninvasive technique in evaluating patients at various stages before, shortly after, and later after percutaneous transluminal coronary angioplasty (PTCA). Coronary restenosis following PTCA occurs at rates between 25% and 40% and currently available screening tests including clinical history, routine exercise electrocardiography, and thallium scintigraphy have proven disappointing correlating with the presence or absence of restenosis. We have found that exercise echocardiography is useful not only in identifying patients who have coronary disease and in predicting the extent and distribution of this disease, but also in demonstrating even very early after angioplasty left ventricular functional improvement both at rest and with exercise. Once patients are discharged from the hospital and followed serially over 5 years, we have found that this tool is extremely valuable in predicting not only coronary restenosis at the site(s) of angioplasty but is also highly predictive of the development of new coronary stenoses. The capabilities of exercise echocardiography to predict restenosis and new disease far exceed the reliability of exercise electrocardiography or the presence or absence of symptoms as indicators of these problems. We have found exercise echocardiography to be an unexcelled screening test in the management of angioplasty patients.

The use of percutaneous transluminal coronary angioplasty in myocardial infarction.

To evaluate the effectiveness of percutaneous transluminal coronary angioplasty (PTCA) in the treatment of myocardial infarction, we reviewed the records of 508 consecutive patients treated within 6 hours of pain onset. Two hundred fifty-eight patients received direct PTCA without thrombolytic therapy, and 250 received thrombolytic therapy followed by immediate PTCA (within 24 hours, n=73) or delayed PTCA (later than 24 hours, n=177). The direct-PTCA group had the lowest initial success rate (92%) and the highest 1-week (8.1%) and 1-year (14%) mortality rates. Immediate PTCA had a 96% success rate, and 6.8% 1-week and 8.2% 1-year mortality rates. Delayed PTCA had the same initial success (96%), but lower 1-week (1.7%) and 1-year (2.3%) mortality. We conclude that both direct PTCA and combination treatment (thrombolytic therapy followed by PTCA) result in high rates of recanalizing occluded coronary arteries, but that combination treatment has higher initial success and survival rates, with delay in the use of PTCA producing the best survival rates.