Neuromental health aspects in adults with CHD after cardiopulmonary bypass intervention during childhood.

OBJECTIVE: It is often assumed, that adult patients with CHD (ACHD) have impairments regarding their cognitive function (CF) and health-related quality of life. In particular, it seems reasonable to assume that cyanosis may have a potential impact on CF as well as surgical or drug treatment into adulthood. This study assesses neuromental health aspects such as CF and health-related quality of life in ACHD patients. METHODS: Seventy-eight ACHD patients (female n = 39 (50%); 34.1 ± 12.9 years; cyanotic CHD n = 49 (62.8%) with a cyanosis duration of 159.8 ± 196.2 month) who underwent open heart surgery as first intervention were asked to participate during routinely follow-up in 2018. Wechsler Intelligence Scale IV was used for CF and the Short Form 36 Health Survey to assess health-related quality of life. RESULTS: Intelligence quotient measures showed significant differences comparing never cyanotic and with a cyanotic phase in verbal comprehension (p = 0.013). There was no association of CF with cyanosis duration, number of surgery or catheter, CHD severity, and time of first surgery. The group of early surgery showed significantly better results in physical function (p = 0.040) of health-related quality of life, and in comparison with their assigned reference, both groups showed significantly reduced results in all domains except in bodily pain and mental health. Full-Scale intelligence quotient correlates with physical function of health-related quality of life. CONCLUSIONS: The results show normal CF in ACHD. Health-related quality of life was weak in comparison with the reference. There is a need to improve the well-being of our ACHD with structured programmes, including physical activity programmes. This growing ACHD population should be focused in order of their needs, medical ones on one hand and on the other hand psychosocial matters.

Anatomy-dependent lung doses from 3D-conformal breast-cancer radiotherapy.

This study aims to identify key anatomic features that govern the individual variability of lung doses from breast-cancer radiotherapy. 3D conformal, intensity-modulated and hybrid techniques with 50.4 Gy whole-breast dose were planned for 128 patients. From their CT images, 17 anatomic measures were assessed and tested as predictors for lung dose-volume characteristics. Tangential techniques yielded mean ipsilateral lung doses in the range of 3-11 Gy. This inter-patient variability was explained to almost 40% by central lung distance, and to almost 60% if this measure was complemented by midplane lung width and maximum heart distance. Also the variability in further dose-volume metrics such as volume fractions receiving 5, 20 or 40 Gy could be largely explained by the anatomy. Multi-field intensity-modulated radiotherapy reduced high-exposed lung volumes, but resulted in higher mean ipsilateral lung doses and larger low-dose burden. Contralateral lung doses ranged from 0.3 to 1 Gy. The results highlight that there are large differences in lung doses among breast-cancer patients. Most of this inter-individual variability can be explained by a few anatomic features. The results will be implemented in a dedicated software tool to provide personalized estimates of long-term health risks related to breast-cancer radiotherapy. The results may also be used to identify favourable as well as problematic anatomies, and serve as a quick quantitative benchmark for individual treatment plans.

Breathing training improves exercise capacity in patients with tetralogy of Fallot: a randomised trial.

OBJECTIVE: Patients with tetralogy of Fallot (ToF) have limited pulmonary blood flow before corrective surgery and ongoing dysfunction of the pulmonary valve and right ventricle throughout life leading to lower exercise capacity and lung volumes in many patients. Inhalation training can increase lung volumes, improve pulmonary blood flow and consequently exercise capacity. This study tests whether home-based daily breathing training improves exercise capacity and lung volumes. METHODS: From February 2017 to November 2018, 60 patients (14.7±4.8 years, 39% female) underwent spirometry (forced vital capacity (FVC); forced expiratory volume in 1 s (FEV1)), cardiopulmonary exercise testing (peak oxygen uptake (peak [Formula: see text]O2)) and breathing excursion measurement. They were randomised into immediate breathing exercise or control group (CG) and re-examined after 6 months. The CG started their training afterwards and were re-examined after further 6 months. Patients trained with an inspiratory volume-oriented breathing device and were encouraged to exercise daily. The primary endpoint of this study was the change in peak [Formula: see text]O2. Results are expressed as mean±SEM (multiple imputations). RESULTS: In the first 6 months (intention to treat analysis), the training group showed a more favourable change in peak [Formula: see text]O2 (Δ0.5±0.6 vs -2.3±0.9 mL/min/kg, p=0.011), FVC (Δ0.18±0.03 vs 0.08±0.03 L, p=0.036) and FEV1 (Δ0.14±0.03 vs -0.00±0.04 L, p=0.007). Including the delayed training data from the CG (n=54), this change in peak [Formula: see text]O2 correlated with self-reported weekly training days (r=0.282, p=0.039). CONCLUSIONS: Daily inspiratory volume-oriented breathing training increases dynamic lung volumes and slows down deconditioning in peak [Formula: see text]O2 in young patients with repaired ToF.

Types of deviation and review criteria in pretreatment central quality control of tumor bed boost in medulloblastoma-an analysis of the German Radiotherapy Quality Control Panel in the SIOP PNET5 MB trial.

PURPOSE: In Germany, Austria, and Switzerland, pretreatment radiotherapy quality control (RT-QC) for tumor bed boost (TB) in non-metastatic medulloblastoma (MB) was not mandatory but was recommended for patients enrolled in the SIOP PNET5 MB trial between 2014 and 2018. This individual case review (ICR) analysis aimed to evaluate types of deviations in the initial plan proposals and develop uniform review criteria for TB boost. PATIENTS AND METHODS: A total of 78 patients were registered in this trial, of whom a subgroup of 65 patients were available for evaluation of the TB treatment plans. Dose uniformity was evaluated according to the definitions of the protocol. Additional RT-QC criteria for standardized review of target contours were elaborated and data evaluated accordingly. RESULTS: Of 65 initial TB plan proposals, 27 (41.5%) revealed deviations of target volume delineation. Deviations according to the dose uniformity criteria were present in 14 (21.5%) TB plans. In 25 (38.5%) cases a modification of the RT plan was recommended. Rejection of the TB plans was rather related to unacceptable target volume delineation than to insufficient dose uniformity. CONCLUSION: In this analysis of pretreatment RT-QC, protocol deviations were present in a high proportion of initial TB plan proposals. These findings emphasize the importance of pretreatment RT-QC in clinical trials for MB. Based on these data, a proposal for RT-QC criteria for tumor bed boost in non-metastatic MB was developed.

Heart atlas for retrospective cardiac dosimetry: a multi-institutional study on interobserver contouring variations and their dosimetric impact.

PURPOSE: Cardiac effects after breast cancer radiation therapy potentially affect more patients as survival improves. The heart's heterogeneous radiation exposure and composition of functional structures call for establishing individual relationships between structure dose and specific late effects. However, valid dosimetry requires reliable contouring which is challenging for small volumes based on older, lower-quality computed tomography imaging. We developed a heart atlas for robust heart contouring in retrospective epidemiologic studies. METHODS AND MATERIALS: The atlas defined the complete heart and geometric surrogate volumes for six cardiac structures: aortic valve, pulmonary valve, all deeper structures combined, myocardium, left anterior myocardium, and right anterior myocardium. We collected treatment planning records from 16 patients from 4 hospitals including dose calculations for 3D conformal tangential field radiation therapy for left-sided breast cancer. Six observers each contoured all patients. We assessed spatial contouring agreement and corresponding dosimetric variability. RESULTS: Contouring agreement for the complete heart was high with a mean Jaccard similarity coefficient (JSC) of 89%, a volume coefficient of variation (CV) of 5.2%, and a mean dose CV of 4.2%. The left (right) anterior myocardium had acceptable agreement with 63% (58%) JSC, 9.8% (11.5%) volume CV, and 11.9% (8.0%) mean dose CV. Dosimetric agreement for the deep structures and aortic valve was good despite higher spatial variation. Low spatial agreement for the pulmonary valve translated to poor dosimetric agreement. CONCLUSIONS: For the purpose of retrospective dosimetry based on older imaging, geometric surrogate volumes for cardiac organs at risk can yield better contouring agreement than anatomical definitions, but retain limitations for small structures like the pulmonary valve.

Pretreatment central quality control for craniospinal irradiation in non-metastatic medulloblastoma : First experiences of the German radiotherapy quality control panel in the SIOP PNET5 MB trial.

PURPOSE: Several studies have demonstrated the negative impact of radiotherapy protocol deviations on tumor control in medulloblastoma. In the SIOP PNET5 MB trial, a pretreatment radiotherapy quality control (RT-QC) program was introduced. A first analysis for patients enrolled in Germany, Switzerland and Austria with focus on types of deviations in the initial plan proposals and review criteria for modern radiation technologies was performed. METHODS AND PATIENTS: Sixty-nine craniospinal irradiation (CSI) plans were available for detailed analyses. RT-QC was performed according to protocol definitions on dose uniformity. Because of the lack of definitions for high-precision 3D conformal radiotherapy within the protocol, additional criteria for RT-QC on delineation and coverage of clinical target volume (CTV) and planning target volume (PTV) were defined and evaluated. RESULTS: Target volume (CTV/PTV) deviations occurred in 49.3% of initial CSI plan proposals (33.3% minor, 15.9% major). Dose uniformity deviations were less frequent (43.5%). Modification of the RT plan was recommended in 43.5% of CSI plans. Unacceptable RT plans were predominantly related to incorrect target delineation rather than dose uniformity. Unacceptable plans were negatively correlated to the number of enrolled patients per institution with a cutoff of 5 patients (p = 0.001). CONCLUSION: This prospective pretreatment individual case review study revealed a high rate of deviations and emphasizes the strong need of pretreatment RT-QC in clinical trials for medulloblastoma. Furthermore, the experiences point out the necessity of new RT-QC criteria for high-precision CSI techniques.

WHAT ANATOMIC FEATURES GOVERN PERSONAL LONG-TERM HEALTH RISKS FROM BREAST CANCER RADIOTHERAPY?

Breast cancer radiotherapy may in the long term lead to radiation-induced secondary cancer or heart disease. These health risks hugely vary among patients, partially due to anatomy-driven differences in doses deposited to the heart, ipsilateral lung and contralateral breast. We identify four anatomic features that largely cover these dosimetric variations to enable personalized risk estimates. For three exemplary, very different risk scenarios, the given parameter set reproduces 63-74% of the individual risk variability for left-sided breast cancer patients. These anatomic features will be used in the PASSOS software to support decision processes in breast-cancer therapy.

Minimum breast distance largely explains individual variability in doses to contralateral breast from breast-cancer radiotherapy.

PURPOSE: To provide personalized estimates of doses to contralateral breast (CB) from breast-cancer radiotherapy. METHODS: Whole-breast irradiations using 3D conformal, intensity-modulated and hybrid techniques with 50.4 Gy prescribed dose were planned for 128 breast-cancer patients. From their CT images, 17 anatomic measures were assessed and tested by model fitting as predictors for CB dose-volume characteristics. RESULTS: Multi-field intensity-modulated radiotherapy (IMRT) yielded mean CB doses of 0.8-7.1 Gy, with no correlation to the studied anatomic parameters. Tangential whole-breast irradiation led to much lower mean CB doses, 0.2-1.6 Gy. About 60% of this inter-patient variability was explained by individual variations in a single anatomic measure, the minimum breast distance (MBD), defined as the CB distance from the tangent to the treated breast. Per 1 cm increase in MBD, the mean CB dose decreased by 10-15%. As an alternative to MBD, dose estimates could be based on the breast-to-breast distance, which is highly correlated with MBD. CONCLUSION: The results enable personalized assessment of CB doses from tangential whole-breast irradiation, based only on parameters assessable from CT data. This may help support clinical decision-making processes as well as analyse retrospective studies on CB risks.

INTER-PATIENT VARIABILITY IN DOSES TO NEARBY ORGANS IN BREAST-CANCER RADIOTHERAPY: INFERENCE FROM ANATOMIC FEATURES.

With improved cure rates and prolonged patient survival after breast-cancer radiotherapy, radiation-induced second cancers and heart diseases become increasingly important. The heart, lungs and contralateral breast are the most critical organs for these long-term effects. Doses to these organs and hence the risks differ between radiotherapy techniques and especially among patients. To address this variability, treatment plans were generated for 128 early-stage breast-cancer patients using intensity-modulated, 3D-conformal and hybrid radiotherapy. Twenty dedicated anatomic measures were assessed from CT data, such as the width and thickness of the treated breast or its distance from the heart. Their impact on doses to critical nearby organs was analysed. The majority of inter-patient variability can be covered with a few anatomic parameters. Patients can thus be stratified according to long-term risks already before treatment planning, and guidance can be provided towards a personalised selection of technique associated with the lowest risk.

LONG-TERM HEALTH RISK AFTER BREAST-CANCER RADIOTHERAPY: OVERVIEW OF PASSOS METHODOLOGY AND SOFTWARE.

Breast-cancer radiotherapy reduces the recurrence rates and improves patient survival. However, it also increases the incidence of second cancers and of heart disease. These radiation-induced long-term health risks become increasingly important with improved cure rates and prolonged patient survival. Radiation doses to nearby as well as distant organs strongly vary between different irradiation techniques and among individual patients. To provide personalized lifetime risk estimates, the German national project PASSOS combines individual anatomy, dosimetric estimates, organ-specific low- and high-dose risk models and personal risk factors such as smoking. A dedicated software tool is under development to assist clinical decision-making processes.

Physical activity in adults with congenital heart disease and associations with functional outcomes.

OBJECTIVE: Improved survival has yielded to growing importance of functional outcome measures in patients with congenital heart disease (CHD). This study applied the International Physical Activity Questionnaire (IPAQ) to assess self-reported physical activity (PA) in patients with CHD and their association with exercise capacity and health-related quality of life (HrQoL). PATIENTS AND METHODS: Prior to cardiopulmonary exercise testing (CPET), 786 consecutive patients (335 female, 31.1±11.6 years) with CHD filled in the short form of the IPAQ and the HrQoL questionnaire 36-Item Short Form. RESULTS: In total, 393 (50.0%) patients reported health-enhancing physical activity (HEPA), 237 (30.2%) minimal activity and 156 (19.8%) inactivity. In comparison with the HEPA group, the inactive group had significant lower peak oxygen uptake (74.2%±20.7% vs 86.8%±22.3%; p<0.001) as well as lower physical (91.0%±16.9% vs 97.4%±13.6%; p<0.001) and mental (97.1%±22.2% vs 104.1%±15.6%; p<0.001) HrQoL. Independent of severity class, surgery, age, beta-blocker, pacemaker and oxygen saturation, the HEPA group in comparison with the inactive group showed significantly less probability for impairments in mental (OR: 0.21, 95% CI: 0.10 to 0.45; p<0.001) and physical (OR: 0.46, 95% CI: 0.23 to 0.92; p=0.027) HrQoL and exercise capacity (OR: 0.36, 95% CI: 0.22 to 0.59; p<0.001). CONCLUSIONS: Categorisation of patientswith CHD with the IPAQ quickly provides clinical information as HEPA patients have a less probability for impaired HrQoL and diminished exercise capacity. Nevertheless, the IPAQ cannot substitute an accelerometer-based assessment for PA, nor a CPET for exercise capacity.