Fractionated stereotactic radiotherapy of intracranial postoperative cavities after resection of brain metastases - Clinical outcome and prognostic factors.

Background and Purpose: After surgical resection of brain metastases (BM), radiotherapy (RT) is indicated. Postoperative stereotactic radiosurgery (SRS) reduces the risk of local progression and neurocognitive decline compared to whole brain radiotherapy (WBRT). Aside from the optimal dose and fractionation, little is known about the combination of systemic therapy and postoperative fractionated stereotactic radiotherapy (fSRT), especially regarding tumour control and toxicity. Methods: In this study, 105 patients receiving postoperative fSRT with 35 Gy in 7 fractions performed with Cyberknife were retrospectively reviewed. Overall survival (OS), local control (LC) and total intracranial brain control (TIBC) were analysed via Kaplan-Meier method. Cox proportional hazards models were used to identify prognostic factors. Results: Median follow-up was 20.8 months. One-year TIBC was 61.6% and one-year LC was 98.6%. Median OS was 28.7 (95%-CI: 16.9-40.5) months. In total, local progression (median time not reached) occurred in 2.0% and in 20.4% radiation-induced contrast enhancements (RICE) of the cavity (after median of 14.3 months) were diagnosed. Absence of extracranial metastases was identified as an independent prognostic factor for superior OS (p = <0.001) in multivariate analyses, while a higher Karnofsky performance score (KPS) was predictive for longer OS in univariate analysis (p = 0.041). Leptomeningeal disease (LMD) developed in 13% of patients. Conclusion: FSRT after surgical resection of BM is an effective and safe treatment approach with excellent local control and acceptable toxicity. Further prospective randomized trials are needed to establish standardized therapeutic guidelines.

Stereotactic ultrahypofractionated MR-guided radiotherapy for localized prostate cancer - Acute toxicity and patient-reported outcomes in the prospective, multicenter SMILE phase II trial.

Background: Due to superior image quality and daily adaptive planning, MR-guided stereotactic body radiation therapy (MRgSBRT) has the potential to further widen the therapeutic window in radiotherapy of localized prostate cancer. This study reports on acute toxicity rates and patient-reported outcomes after MR-guided adaptive ultrahypofractionated radiotherapy for localized prostate cancer within the prospective, multicenter phase II SMILE trial. Materials and methods: A total of 69 patients with localized prostate cancer underwent MRgSBRT with daily online plan adaptation. Inclusion criteria comprised a tumor stage ≤ T3a, serum PSA value ≤ 20 ng/ml, ISUP Grade group ≤ 4. A dose of 37.5 Gy was prescribed to the PTV in five fractions on alternating days with an optional simultaneous boost of 40 Gy to the dominant intraprostatic lesion defined by multiparametric MRI. Acute genitourinary (GU-) and gastrointestinal (GI-) toxicity, as defined by CTCAE v. 5.0 and RTOG as well as patient-reported outcomes according to EORTC QLQ-C30 and -PR25 scores were analyzed at completion of radiotherapy, 6 and 12 weeks after radiotherapy and compared to baseline symptoms. Results: There were no toxicity-related treatment discontinuations. At the 12-week follow-up visit, no grade 3 + toxicities were reported according to CTCAE. Up until the 12-week visit, in total 16 patients (23 %) experienced a grade 2 GU or GI toxicity. Toxicity rates peaked at the end of radiation therapy and subsided within the 12-week follow-up period. At the 12-week follow-up visit, no residual grade 2 GU toxicities were reported and 1 patient (1 %) had residual grade 2 enteritic symptoms. With exception to a significant improvement in the emotional functioning score following MRgSBRT, no clinically meaningful changes in the global health status nor in relevant subscores were reported. Conclusion: Daily online-adaptive MRgSBRT for localized prostate cancer resulted in an excellent overall toxicity profile without any major negative impact on quality of life.

Practice, play, repeat - individualized outcomes after the "intensity matters!"-program for children with disabilities - a descriptive multicase study.

PURPOSE: To examine and categorize individual outcomes after the "Intensity matters!"-program, a new, cross-professional intensive intervention for children with disabilities across Norway. MATERIALS AND METHODS: 84 children and their parents/legal guardian were enrolled in this multicase study. Participants were active in defining goals, and hereby the content of the intervention. The pre-settled goals were grouped into the categories of body functions and structure, activities and participation inspired by the components of the International Classification of Functioning, Disability, and Health (ICF). The pre-settled goals were assessed pre- and post-intervention by using The Canadian Occupational Performance Measure (COPM). A clinically important change was predefined as a change ≥2 points. RESULTS: 1004 pre-settled goals were categorized into focus areas, where 62.4% were categorized as activity; functional mobility (n = 626). Post-intervention assessment of the COPM ratings of child performance and satisfaction showed a mean change of 3.7 (range -0.25;8.5) and 3.8 (range 0.25;10), respectively. CONCLUSION: The majority of participants in the "Intensity Matters!"-program had a clinically important change in their individual goals after only three weeks of intervention. This study supports the use of client-centered measures in rehabilitation for children with disabilities, but a further examination of long-term outcome is warranted.

The "Intensity matters!"-program is a cross-professional, goal-directed, and intensive intervention with a high degree of user involvement.In a sample of 84 individual participants, this study shows that the majority of focus areas were found to be of clinically relevant improvement post intervention.Individual structured programs with high intensity in a group setting are likely to be successful for children with different health conditions, including cerebral palsy and other neurological or genetic disorders.Areas of concern formulated ahead of a three-week, intensive, goal-directed program were mainly linked to the ICF domain activity, and more specifically related to personal care and functional mobility.Rehabilitation professionals should emphasise participants' priorities and involvement of children when planning and evaluating a therapeutic intervention.

Stereotactic MRI-guided radiation therapy for localized prostate cancer (SMILE): a prospective, multicentric phase-II-trial.

BACKGROUND: Normofractionated radiation regimes for definitive prostate cancer treatment usually extend over 7-8 weeks. Recently, moderate hypofractionation with doses per fraction between 2.2 and 4 Gy has been shown to be safe and feasible with oncologic non-inferiority compared to normofractionation. Radiobiologic considerations lead to the assumption that prostate cancer might benefit in particular from hypofractionation in terms of tumor control and toxicity. First data related to ultrahypofractionation demonstrate that the overall treatment time can be reduced to 5-7 fractions with single doses > 6 Gy safely, even with simultaneous focal boosting of macroscopic tumor(s). With MR-guided linear accelerators (MR-linacs) entering clinical routine, invasive fiducial implantations become unnecessary. The aim of the multicentric SMILE study is to evaluate the use of MRI-guided stereotactic radiotherapy for localized prostate cancer in 5 fractions regarding safety and feasibility. METHODS: The study is designed as a prospective, one-armed, two-stage, multi-center phase-II-trial with 68 patients planned. Low- and intermediate-risk localized prostate cancer patients will be eligible for the study as well as early high-risk patients (cT3a and/or Gleason Score ≤ 8 and/or PSA ≤ 20 ng/ml) according to d'Amico. All patients will receive definitive MRI-guided stereotactic radiation therapy with a total dose of 37.5 Gy in 5 fractions (single dose 7.5 Gy) on alternating days. A focal simultaneous integrated boost to MRI-defined tumor(s) up to 40 Gy can optionally be applied. The primary composite endpoint includes the assessment of urogenital or gastrointestinal toxicity ≥ grade 2 or treatment-related discontinuation of therapy. The use of MRI-guided radiotherapy enables online plan adaptation and intrafractional gating to ensure optimal target volume coverage and protection of organs at risk. DISCUSSION: With moderate hypofractionation being the standard in definitive radiation therapy for localized prostate cancer at many institutions, ultrahypofractionation could be the next step towards reducing treatment time without compromising oncologic outcomes and toxicities. MRI-guided radiotherapy could qualify as an advantageous tool as no invasive procedures have to precede in therapeutic workflows. Furthermore, MRI guidance combined with gating and plan adaptation might be essential in order to increase treatment effectivity and reduce toxicity at the same time.

MR-guided adaptive versus ITV-based stereotactic body radiotherapy for hepatic metastases (MAESTRO): a randomized controlled phase II trial.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an established local treatment method for patients with hepatic oligometastasis or oligoprogression. Liver metastases often occur in close proximity to radiosensitive organs at risk (OARs). This limits the possibility to apply sufficiently high doses needed for optimal local control. Online MR-guided radiotherapy (oMRgRT) is expected to hold potential to improve hepatic SBRT by offering superior soft-tissue contrast for enhanced target identification as well as the benefit of gating and daily real-time adaptive treatment. The MAESTRO trial therefore aims to assess the potential advantages of adaptive, gated MR-guided SBRT compared to conventional SBRT at a standard linac using an ITV (internal target volume) approach. METHODS: This trial is conducted as a prospective, randomized, three-armed phase II study in 82 patients with hepatic metastases (solid malignant tumor, 1-3 hepatic metastases confirmed by magnetic resonance imaging (MRI), maximum diameter of each metastasis ≤ 5 cm (in case of 3 metastases: sum of diameters ≤ 12 cm), age ≥ 18 years, Karnofsky Performance Score ≥ 60%). If a biologically effective dose (BED) ≥ 100 Gy (α/ß = 10 Gy) is feasible based on ITV-based planning, patients will be randomized to either MRgRT or ITV-based SBRT. If a lesion cannot be treated with a BED ≥ 100 Gy, the patient will be treated with MRgRT at the highest possible dose. Primary endpoint is the non-inferiority of MRgRT at the MRIdian Linac® system compared to ITV-based SBRT regarding hepatobiliary and gastrointestinal toxicity CTCAE III or higher. Secondary outcomes investigated are local, locoregional (intrahepatic) and distant tumor control, progression-free survival, overall survival, possible increase of BED using MRgRT if the BED is limited with ITV-based SBRT, treatment-related toxicity, quality of life, dosimetric parameters of radiotherapy plans as well as morphological and functional changes in MRI. Potential prognostic biomarkers will also be evaluated. DISCUSSION: MRgRT is known to be both highly cost- and labor-intensive. The MAESTRO trial aims to provide randomized, higher-level evidence for the dosimetric and possible consecutive clinical benefit of MR-guided, on-table adaptive and gated SBRT for dose escalation in critically located hepatic metastases adjacent to radiosensitive OARs. TRIAL REGISTRATION: The study has been prospectively registered on August 30th, 2021: Clinicaltrials.gov, "Magnetic Resonance-guided Adaptive Stereotactic Body Radiotherapy for Hepatic Metastases (MAESTRO)", NCT05027711.

MR-guided adaptive stereotactic body radiotherapy (SBRT) of primary tumor for pain control in metastatic pancreatic ductal adenocarcinoma (mPDAC): an open randomized, multicentric, parallel group clinical trial (MASPAC).

BACKGROUND: Pain symptoms in the upper abdomen and back are prevalent in 80% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), where the current standard treatment is a systemic therapy consisting of at least doublet-chemotherapy for fit patients. Palliative low-dose radiotherapy is a well-established local treatment option but there is some evidence for a better and longer pain response after a dose-intensified radiotherapy of the primary pancreatic cancer (pPCa). Stereotactic body radiation therapy (SBRT) can deliver high radiation doses in few fractions, therefore reducing chemotherapy-free intervals. However, prospective data on pain control after SBRT of pPCa is very limited. Therefore, we aim to investigate the impact of SBRT on pain control in patients with mPDAC in a prospective trial. METHODS: This is a prospective, double-arm, randomized controlled, international multicenter study testing the added benefit of MR-guided adaptive SBRT of the pPca embedded between standard of care-chemotherapy (SoC-CT) cycles for pain control and prevention of pain in patients with mPDAC. 92 patients with histologically proven mPDAC and at least stable disease after initial 8 weeks of SoC-CT will be eligible for the trial and 1:1 randomized in 3 centers in Germany and Switzerland to either experimental arm A, receiving MR-guided SBRT of the pPCa with 5 × 6.6 Gy at 80% isodose with continuation of SoC-CT thereafter, or control arm B, continuing SoC-CT without SBRT. Daily MR-guided plan adaptation intents to achieve good target coverage, while simultaneously minimizing dose to organs at risk. Patients will be followed up for minimum 6 and maximum of 18 months. The primary endpoint of the study is the "mean cumulative pain index" rated every 4 weeks until death or end of study using numeric rating scale. DISCUSSION: An adequate long-term control of pain symptoms in patients with mPDAC is an unmet clinical need. Despite improvements in systemic treatment, local complications due to pPCa remain a clinical challenge. We hypothesize that patients with mPDAC will benefit from a local treatment of the pPCa by MR-guided SBRT in terms of a durable pain control with a simultaneously favorable safe toxicity profile translating into an improvement of quality-of-life. TRIAL REGISTRATION: German Registry for Clinical Trials (DRKS): DRKS00025801. Meanwhile the study is also registered at ClinicalTrials.gov with the Identifier: NCT05114213.

[Magnetic-resonance-guided radiotherapy : The beginning of a new era in radiation oncology?] / Magnetresonanzgeführte Strahlentherapie : Beginn einer neuen Ära in der Radioonkologie?

CLINICAL ISSUE: Image-guided radiotherapy (IGRT) using X­rays and cone-beam computed tomography (CT) has fostered precision radiotherapy. However, inter- and intrafractional variations of target volume position and organs at risk still limit target volume dose and sparing of radiosensitive organs at risk. METHODOLOGICAL INNOVATIONS: Hybrid machines directly combining linear accelerators and magnetic resonance (MR) imaging allow for live imaging during radiotherapy. PERFORMANCE: Besides highly improved soft tissue contrast, MR-linacs enable online, on-table adaptive radiotherapy. Thus, adaptation of the treatment plan to the anatomy of the day, dose escalation and superior sparing of organs at risk become possible. ACHIEVEMENTS: This article summarizes the underlying intention for the development of MR-guided radiotherapy, technical innovations and challenges as well as the current state-of-the-art. Potential clinical benefits and future developments are discussed. PRACTICAL RECOMMENDATIONS: Increasing availability of MR imaging at linear accelerators calls for the ability to review and interpret MR images. Therefore, close collaborations of diagnostic radiologists and radiation oncologists are mandatory to foster this fascinating technique.

MR-guidance in clinical reality: current treatment challenges and future perspectives.

Magnetic Resonance-guided radiotherapy (MRgRT) marks the beginning of a new era. MR is a versatile and suitable imaging modality for radiotherapy, as it enables direct visualization of the tumor and the surrounding organs at risk. Moreover, MRgRT provides real-time imaging to characterize and eventually track anatomical motion. Nevertheless, the successful translation of new technologies into clinical practice remains challenging. To date, the initial availability of next-generation hybrid MR-linac (MRL) systems is still limited and therefore, the focus of the present preview was on the initial applicability in current clinical practice and on future perspectives of this new technology for different treatment sites.MRgRT can be considered a groundbreaking new technology that is capable of creating new perspectives towards an individualized, patient-oriented planning and treatment approach, especially due to the ability to use daily online adaptation strategies. Furthermore, MRL systems overcome the limitations of conventional image-guided radiotherapy, especially in soft tissue, where target and organs at risk need accurate definition. Nevertheless, some concerns remain regarding the additional time needed to re-optimize dose distributions online, the reliability of the gating and tracking procedures and the interpretation of functional MR imaging markers and their potential changes during the course of treatment. Due to its continuous technological improvement and rapid clinical large-scale application in several anatomical settings, further studies may confirm the potential disruptive role of MRgRT in the evolving oncological environment.

The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases.

BACKGROUND: The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. METHODS: The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. RESULTS: Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. CONCLUSION: In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.

Stereotactic body radiotherapy (SBRT) for multiple pulmonary oligometastases: Analysis of number and timing of repeat SBRT as impact factors on treatment safety and efficacy.

BACKGROUND: Stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by an excellent safety profile; however, experiences are mostly based on treatment of one single metastasis. It was the aim of this study to evaluate safety and efficacy of SBRT for multiple pulmonary metastases. PATIENTS AND METHODS: This study is based on a retrospective database of the DEGRO stereotactic working group, consisting of 637 patients with 858 treatments. Cox regression and logistic regression were used to analyze the association between the number of SBRT treatments or the number and the timing of repeat SBRT courses with overall survival (OS) and the risk of early death. RESULTS: Out of 637 patients, 145 patients were treated for multiple pulmonary metastases; 88 patients received all SBRT treatments within one month whereas 57 patients were treated with repeat SBRT separated by at least one month. Median OS for the total patient population was 23.5 months and OS was not significantly influenced by the overall number of SBRT treatments or the number and timing of repeat SBRT courses. The risk of early death within 3 and 6 months was not increased in patients treated with multiple SBRT treatments, and no grade 4 or grade 5 toxicity was observed in these patients. CONCLUSIONS: In appropriately selected patients, synchronous SBRT for multiple pulmonary oligometastases and repeat SBRT may have a comparable safety and efficacy profile compared to SBRT for one single oligometastasis.

Nomogram based overall survival prediction in stereotactic body radiotherapy for oligo-metastatic lung disease.

BACKGROUND: Radical local treatment of pulmonary metastases is practiced with increasing frequency due to acknowledgment and better understanding of oligo-metastatic disease. This study aimed to develop a nomogram predicting overall survival (OS) after stereotactic body radiotherapy (SBRT) for pulmonary metastases. PATIENTS AND METHODS: A multi-institutional database of 670 patients treated with SBRT for pulmonary metastases was used as training cohort. Cox regression analysis with bidirectional variable elimination was performed to identify factors to be included into the nomogram model to predict 2-year OS. The calibration rate of the nomogram was assessed by plotting the actual Kaplan-Meier 2-year OS against the nomogram predicted survival. The nomogram was externally validated using two separate monocentric databases of 145 and 92 patients treated with SBRT for pulmonary metastases. RESULTS: The median follow up of the trainings cohort was 14.3months, the 2-year and 5-year OS was 52.6% and 23.7%, respectively. Karnofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the largest treated metastasis and number of metastases (1 versus >1) were significant prognostic factors in the Cox model (all p<0.05). The calculated concordance-index for the nomogram was 0.73 (concordance indexes of all prognostic factors between 0.54 and 0.6). Based on the nomogram the training cohort was divided into 4 groups and 2-year OS ranged between 24.2% and 76.1% (predicted OS between 30.2% and 78.4%). The nomogram discriminated between risk groups in the two validation cohorts (concordance index 0.68 and 0.67). CONCLUSIONS: A nomogram for prediction of OS after SBRT for pulmonary metastases was generated and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting. KEY MESSAGE: A nomogram for prediction of overall survival after stereotactic body radiotherapy (SBRT) for pulmonary metastases was developed and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting.

Radiosurgery with flattening-filter-free techniques in the treatment of brain metastases : Plan comparison and early clinical evaluation.

BACKGROUND: Radiosurgical treatment of brain metastases is well established in daily clinical routine. Utilization of flattening-filter-free beams (FFF) may allow for more rapid delivery of treatment doses and improve clinical comfort. Hence, we compared plan quality and efficiency of radiosurgery in FFF mode to FF techniques. MATERIALS AND METHODS: Between November 2014 and June 2015, 21 consecutive patients with 25 brain metastases were treated with stereotactic radiosurgery (SRS) in FFF mode. Brain metastases received dose-fractionation schedules of 1 × 20 Gy or 1 × 18 Gy, delivered to the conformally enclosing 80 % isodose. Three patients with critically localized or large (>3 cm) brain metastases were treated with 6 × 5 Gy. Plan quality and efficiency were evaluated by analyzing conformity, dose gradients, dose to healthy brain tissue, treatment delivery time, and number of monitor units. FFF plans were compared to those using the FF method, and early clinical outcome and toxicity were assessed. RESULTS: FFF mode resulted in significant reductions in beam-on time (p < 0.001) and mean brain dose (p = 0.001) relative to FF-mode comparison plans. Furthermore, significant improvements in dose gradients and sharper dose falloffs were found for SRS in FFF mode (-1.1 %, -29.6 %; p ≤ 0.003), but conformity was slightly superior in SRS in FF mode (-1.3 %; p = 0.001). With a median follow-up time of 5.1 months, 6­month overall survival was 63.3 %. Local control was observed in 24 of 25 brain metastases (96 %). CONCLUSION: SRS in FFF mode is time efficient and provides similar plan quality with the opportunity of slightly reduced dose exposure to healthy brain tissue when compared to SRS in FF mode. Clinical outcomes appear promising and show only modest treatment-related toxicity.

Intensity-modulated proton therapy, volumetric-modulated arc therapy, and 3D conformal radiotherapy in anaplastic astrocytoma and glioblastoma : A dosimetric comparison.

PURPOSE: The prognosis for high-grade glioma (HGG) patients is poor; thus, treatment-related side effects need to be minimized to conserve quality of life and functionality. Advanced techniques such as proton radiation therapy (PRT) and volumetric-modulated arc therapy (VMAT) may potentially further reduce the frequency and severity of radiogenic impairment. MATERIALS AND METHODS: We retrospectively assessed 12 HGG patients who had undergone postoperative intensity-modulated proton therapy (IMPT). VMAT and 3D conformal radiotherapy (3D-CRT) plans were generated and optimized for comparison after contouring crucial neuronal structures important for neurogenesis and neurocognitive function. Integral dose (ID), homogeneity index (HI), and inhomogeneity coefficient (IC) were calculated from dose statistics. Toxicity data were evaluated. RESULTS: Target volume coverage was comparable for all three modalities. Compared to 3D-CRT and VMAT, PRT showed statistically significant reductions (p < 0.05) in mean dose to whole brain (-20.2 %, -22.7 %); supratentorial (-14.2 %, -20,8 %) and infratentorial (-91.0 %, -77.0 %) regions; brainstem (-67.6 %, -28.1 %); pituitary gland (-52.9 %, -52.5 %); contralateral hippocampus (-98.9 %, -98.7 %); and contralateral subventricular zone (-62.7 %, -66.7 %, respectively). Fatigue (91.7 %), radiation dermatitis (75.0 %), focal alopecia (100.0 %), nausea (41.7 %), cephalgia (58.3 %), and transient cerebral edema (16.7 %) were the most common acute toxicities. CONCLUSION: Essential dose reduction while maintaining equal target volume coverage was observed using PRT, particularly in contralaterally located critical neuronal structures, areas of neurogenesis, and structures of neurocognitive functions. These findings were supported by preliminary clinical results confirming the safety and feasibility of PRT in HGG.

MSCT guided sizing of the Edwards Sapien XT TAVI device: impact of different degrees of oversizing on clinical outcome.

AIMS: Prospective data on the usage of 3-dimensional imaging based annulus sizing on the outcome of TAVI is not available yet and there is general uncertainty about the optimal degree of oversizing. In the current study we therefore assessed a 3-D MSCT guided over-sizing approach and evaluated the clinical outcome of different degrees of oversizing. METHODS: TAVI-size-selection was done using systolic MSCT-annulus cross-sectional-area (CSA) measurements in 107 patients with severe aortic stenosis with the goal to oversize the 3rd generation balloon expandable Edwards Sapien XT (ESTV) device in relation to the native aortic annulus CSA. RESULTS: Among different degrees of oversizing there were no differences in the occurrence of stroke, myocardial infarction and death. No aortic injuries were observed. The overall rate of >mild postprocedural aortic regurgitation (PAR) was 7.6%. Increasing oversizing ratios are associated with lower rates of >mild PAR (r = -0.236, p<0.02) with the lowest rate of >mild PAR in patients with area based oversizing ratios >25% and the highest rate in patients with oversizing ratios <15% (0% vs. 15.8%, p<0.02). The rate of postprocedural permanent pacemakers tended to be lower in patients with <15% oversizing compared to those with >25% oversizing (5.3 vs. 16.7%, p<0.23). CONCLUSIONS: MSCT guided ESTV-device sizing is safe and is associated with significantly lower than previously reported rates for PAR. A device/annulus oversizing ratio of 15-25% based on area and 7-12% based on mean diameter appears to provide the best risk-benefit ratio in terms of PAR reduction and conduction disorders.

[Intravascular imaging and its integration into coronary angiography]. / Intravaskuläre Bildgebung und Integration in die moderne Herzkatheterdiagnostik.

Despite technical innovations of non-invasive coronary imaging modalities, coronary angiography still remains the standard of reference for the assessment of CAD.The advances in interventional cardiology require also increased imaging capabilities, which cannot be fully addressed by conventional coronary angiography. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) as well as near infrared spectroscopy (NIRS) are important developments and will be covered in this review article.IVUS was already around in interventional cardiology since the 90ies. It was the first to offer a high resolution tomographic image of the coronary arteries in vivo. Beyond that, it is also frequently used for peri- and postprocedural imaging. Furthermore, the radiofrequency information ("virtual histology") can be applied to perform a basic tissue characterization.Using near coherent light instead of ultrasound, optical coherence tomography (OCT) is able to deliver a 10 fold higher resolution compared to IVUS when imaging coronary plaques.This allows also for the detection of potential vulnerable lesions as well as for the detection of neo-intimal stent strut coverage following stent placement.Using near infrared spectroscopy (NIRS) even insights into the chemical composition of coronary plaques can be achieved.The development of advanced image acquisition technologies enables us to combine modern intravascular imaging technologies and conventional coronary angiography and hereby achieve additional benefit.

Influence of age on pain perception in acute myocardial ischemia: a possible cause for delayed treatment in elderly patients.

BACKGROUND: Elderly patients tend to seek later for medical help during myocardial infarction. This may be caused by impaired pain perception with ageing. The aim of our study was to prospectively evaluate age-dependent differences in pain perception during temporary induced coronary ischemia. METHODS: In 102 patients (68 male, age 68±11 years) undergoing percutaneous coronary intervention, ischemia was induced by balloon inflation for up to 120 s. Time to onset of perceived pain, pain characteristics and pain severity (0=no pain, 100=worst pain possible) was registered. This was repeated twice to evaluate ischemic preconditioning. A 12 lead ECG-tracing was simultaneously recorded. Patients were divided by their median age into 2 groups with comparable demographics: ≤69 years (group 1) and >69 years (group 2). RESULTS: Group 1 patients demonstrated earlier onset of pain (most apparent during the second inflation: 31±15 s vs. 46±26 s; p<0.001), and greater pain severity (inflation #1: 64±21 vs. 51±25 [p=0.017]; #2: 66±23 vs.52±27 [p=0.008]; #3: 63±23 vs. 54±24 [p=0.085]). ST-changes did not differ (0.24±0.10 vs. 0.20±0.14, [p=0.18]; 0.27±0.17 vs. 0.20±0.14, [p=0.11]; 0.19±0.13 vs. 0.16±0.09; [p=0.32]). Time from occlusion to onset of ECG changes did not differ between the groups, but increased with repetitive inflations (inflation #1: 29±11 s vs. 29±11 s; #2: 31±14 vs. 33±11; #3: 39±21 vs. 40±15 s [increase p=0.017; p<0.001]). CONCLUSION: These data suggest that the perception of pain from myocardial ischemia in the elderly is significantly less severe and delayed compared to younger patients.

Clinical outcome and quality of life after interventional treatment of left main disease with drug-eluting-stents in comparison to CABG in elderly and younger patients.

INTRODUCTION: The aim of this study was to prospectively assess the clinical outcome and quality of life of elderly patients who underwent either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) with drug-eluting stents (DES) for treatment of significant left main disease (LMD) compared to a younger patient population. METHODS: Consecutive patients, admitted into our institution between 04/2004 and 12/2007 with LMD and a life expectancy of >1 year were prospectively included and stratified in two groups (either CABG or left main stenting [LMS] with DES) based on the patients' age at inclusion (> or ≤75 years). Rates of death, myocardial infarction (MI), stroke, and target lesion revascularization (TLR) were evaluated over a 12 month follow-up. Six months after the initial procedure, additionally, quality of life was assessed using the SF-36 questionnaire. RESULTS: A total of 300 patients was included; 56 of the 95 PCI patients (59%) were ≤75 years and 39 (44%) >75 years, whereas 155 of 205 patients in the CABG group were ≤75 years (76%), and 50 patients (24%) were >75 years. Mean follow-up was 312 ± 226 days in the PCI and 377 ± 286 in the CABG group. Rates of death and MI were not significantly different between the four groups at the end of follow-up. There was no difference in quality of life after 6 months. CONCLUSION: In this prospective trial, PCI of LM with DES in elderly patients was feasible with a short- and intermediate term outcome comparable to CABG procedure and to a younger patient cohort.

New X-ray imaging modalities and their integration with intravascular imaging and interventions.

During recent years various techniques emerged providing more detailed images and insights in the cardiovascular system. C-Arm computed tomography is currently introduced in cardiac imaging offering the potential of three dimensional imaging of the coronary arteries, the cardiac chambers, venous system and a variety of anatomic anomalies inside the interventional environment. Furthermore it might enable perfusion imaging during percutaneous coronary intervention (PCI). Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are meanwhile established tools for detailed assessment of the coronary arteries. Their use might further increase with automated tissue characterization, three dimensional reconstruction, integration in angiography systems, and new emerging techniques. Parameters of fluid tissue interactions are important factors in the pathogenesis of atherosclerosis. These parameters can be calculated using computational fluid dynamics based on three dimensional models of the coronary vessels which can be derived from various sources including multislice computed tomography (MSCT), C-Arm CT or 3D reconstructed IVUS or OCT. Their use in the clinical setting has yet to be determined especially with regard to their ability in increasing treatment efficiency and clinical outcome.

[Application of C-arm computed tomography in cardiology]. / Kardiale Anwendung der C-Arm-Computertomographie.

C-arm computed tomography is currently being introduced into cardiac imaging and offers the potential for three-dimensional imaging of the cardiac anatomy within the interventional environment. This detailed view is necessary to support complex interventional strategies, such as transcutaneous valve replacement, interventional therapy of atrial fibrillation, implantation of biventricular pacemakers and assessment of myocardial perfusion. Currently, the major limitation of this technology is its insufficient temporal resolution which limits the visualization of fast moving parts of the heart.

[Intravascular optical coherence tomography: differentiation of atherosclerotic plaques and quantification of vessel dimensions in crural arterial specimens]. / Intravaskuläre optische Kohärenztomographie: Unterscheidung verschiedener Plaquetypen und Vermessung von Gefässdimensionen in atherosklerotischen Unterschenkelarterien.

PURPOSE: Intravascular optical coherence tomography (OCT) is a new technique based on infrared light that visualizes the arteries with a resolution of 10-20 microm. Intravascular ultrasound (IVUS) is the current in vivo reference standard and provides a resolution of 100-150 microm. This study compared OCT to IVUS and histopathology with respect to the ability to differentiate atherosclerotic plaques and quantify vascular dimensions in peripheral crural arteries ex vivo. MATERIALS AND METHODS: 50 segments of atherosclerotic arteries derived from five amputated human lower extremities were examined. The different plaque types (fibrous, high-lipid content, calcified) were assigned by two independent examiners, and the sensitivity and specificity of OCT in comparison with histopathology as well as intra- and interobserver consensus were calculated. A comparison of OCT with IVUS addressed the parameters: luminal area (LA), vascular wall area (VA) and plaque area (PA). RESULTS: When comparing OCT and histopathology with respect to the differentiation of various plaque types, sensitivities of 81 % and specificities of 89 % for fibrous plaques, of 100 % and 93 % for lipid-rich plaques and of 80 % and 89 % for calcified plaques were achieved (overall correlation 83 %). Intra- and interobserver consensus was very high (kappa = 0.86 and kappa = 0.89, p < 0.001, respectively). There was also a high correlation between quantitative measurements (Bland-Altman plot [LA]: mean bias, 0.1 mm(2) accuracy +/- 1.8 mm(2), r = 0.95 [p < 0.001] Bland-Altman plot [VA]: mean bias, 0.3 mm(2) accuracy +/- 2.3 mm(2), r = 0.94 [p < 0.001] Bland-Altman plot [PA]: mean bias, 0.4 mm(2) accuracy +/- 2.3 mm(2), r = 0.80 [p < 0.01]. CONCLUSION: OCT allows the differentiation of atherosclerotic plaque types in crural arteries with high accuracy compared to histopathology. Quantitative measurements show a high correlation with IVUS, the current reference standard.