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.

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.

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.

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.

Severe aortic insufficiency in juvenile chronic arthritis.

Valvular heart disease is rare in patients with juvenile chronic arthritis. We describe a 27-year-old woman with the systemic-onset form of juvenile chronic arthritis in whom aortic insufficiency necessitated valve replacement. Nodules were seen on both the aortic and anterior mitral leaflets at surgery, and histopathologic evaluation of the excised aortic leaflets demonstrated nonspecific changes similar to those described in rheumatoid valve disease causing aortic insufficiency in adults with rheumatoid arthritis. We believe that this is the first reported case of aortic insufficiency in systemic-onset juvenile chronic arthritis in which the pathologic condition of the valve can be attributed to the underlying disease.