Matthias Rief

Can Tyrosine Kinase Inhibitors be Discontinued in Patients with Metastatic Renal Cell Carcinoma and a Complete Response to Treatment? A Multicentre, Retrospective Analysis

BACKGROUND Discontinuation of treatment with tyrosine kinase inhibitors (TKIs) and readministration in case of recurrence could improve quality of life (QoL) and reduce treatment costs for patients with metastatic renal cell carcinoma (mRCC) in which a complete remission (CR) is achieved by medical treatment alone or with additional resection of residual metastases. OBJECTIVE To evaluate whether TKIs can be discontinued in these selected patients with mRCC. DESIGN, SETTING, AND PARTICIPANTS A retrospective analysis of medical records and imaging studies was performed on all patients with mRCC treated with TKIs (n=266) in five institutions. Patients with a CR under TKI treatment alone or with additional metastasectomy of residual disease following a partial response (PR), in which TKIs were discontinued, were included in the analysis. Outcome criteria analysed were time to recurrence of previous metastases, occurrence of new metastases, symptomatic progression, improvement of adverse events, and response to reexposure to TKIs. INTERVENTIONS Sunitinib 50mg/day for 4 wk on and 2 wk off, sorafenib 800mg/day. MEASUREMENTS Response according to Response Evaluation Criteria in Solid Tumours (RECIST). RESULTS AND LIMITATIONS We identified 12 cases: 5 CRs with sunitinib, 1 CR with sorafenib, and 6 surgical CRs with sunitinib followed by residual metastasectomy. Side-effects subsided in all patients off treatment. At a median follow-up of 8.5 mo (range: 4-25) from TKI discontinuation, 7 of 12 patients remained without recurrence and 5 had recurrent disease, with new metastases in 3 cases. Median time to progression was 6 mo (range: 3-8). Readministration of TKI was effective in all cases. The study is limited by small numbers and retrospective design. CONCLUSIONS Discontinuation of TKI in patients with mRCC and CR carries the risk of progression with new metastases and potential complications. Further investigation in a larger cohort of patients is warranted before such an approach can be regarded as safe.

Computed Tomography Angiography and Myocardial Computed Tomography Perfusion in Patients With Coronary Stents: Prospective Intraindividual Comparison With Conventional Coronary Angiography

OBJECTIVES This study sought to determine whether adding myocardial computed tomography perfusion (CTP) to computed tomography angiography (CTA) improves diagnostic performance for coronary stents. BACKGROUND CTA of coronary stents has been limited by nondiagnostic studies caused by metallic stent material and coronary motion. METHODS CTA and CTP were performed in 91 consecutive patients with stents before quantitative coronary angiography, the reference standard for obstructive stenosis (≥50%). If a coronary stent or vessel was nondiagnostic on CTA, adenosine stress CTP in the corresponding myocardial territory was read for combined CTA/CTP. RESULTS Patients had an average of 2.5 ± 1.8 coronary stents (1 to 10), with a diameter of 3.0 ± 0.5 mm. Significantly more patients were nondiagnostic for stent assessment by CTA (22%; mainly due to metal artifacts [75%] or motion [25%]) versus CTP (1%; p < 0.001; severe angina precluded CTP in 1 case). The per-patient diagnostic accuracy of CTA/CTP for stents (87%, 95% confidence interval [CI]: 78% to 93%) was significantly higher than that of CTA alone (71%, 95% CI: 61% to 80%; p < 0.001), mainly because nondiagnostic examinations were significantly reduced (p < 0.001). In the analysis of any coronary artery disease, diagnostic accuracy and nondiagnostic rate were also significantly improved by the addition of CTP (p < 0.001). CTA/CTP (7.9 ± 2.8 mSv) had a significantly lower effective radiation dose than angiography (9.5 ± 5.1 mSv; p = 0.005). The area under the receiver-operating characteristic curve for CTA/CTP (0.82, 95% CI: 0.69 to 0.95) was superior to that for CTA (0.69, 95% CI: 0.57 to 0.82; p < 0.001) in identifying patients requiring stent revascularization. CONCLUSIONS Combined coronary CTA and myocardial CTP improves diagnosis of CAD and in-stent restenosis in patients with stents compared with CTA alone. (Coronary Artery Stent Evaluation With 320-Slice Computed Tomography-The CArS 320 Study [CARS-320]; NCT00967876).

High Spatial Resolution T1-weighted Mr Imaging of Liver and Biliary Tract During Uptake Phase of a Hepatocyte-specific Contrast Medium

Objectives:The hypothesis for this prospective study was that T1-weighted respiratory triggered high spatial resolution images of the liver acquired during the uptake phase of a hepatobiliary contrast medium are technically feasible and provide significantly improved image quality compared with breath-hold images. Materials and Methods:An inversion recovery-prepared spoiled gradient echo sequence was developed that can be obtained with respiratory triggering. This sequence was acquired in 20 patients with a total of 41 focal liver lesions and compared with axial and coronal breath-hold spoiled gradient echo sequences. All 3 sequences were obtained in the hepatobiliary phase after intravenous injection of Gd-EOB-DTPA at a dosage of 0.025 mmol/kg of body weight. Quantitative evaluation measured the contour sharpness index of the common bile duct and calculated the relative contrast between liver lesions (common bile duct, respectively) and liver parenchyma. In the qualitative assessment, 2 readers independently scored the depiction of focal liver lesions and 3 segments of the biliary tract, the sharpness of hepatic vessels, and the level of artifacts. Statistical significance was assumed at P < 0.05. Results:The respiratory-triggered sequence was technically successful in all 20 patients, revealed significantly higher liver-lesion contrast, contour-sharpness index and scores for depiction of focal liver lesions, biliary tree, and sharpness of hepatic vessels compared with the respective breath-hold sequence. The relative contrast between the common bile duct and the liver parenchyma was significantly higher for the coronal breath-hold sequence compared with the respiratory-triggered sequence. No significant difference was found with respect to the level of artifacts. The 2 readers agreed in 77.9% of the qualitative assessments. Conclusions:T1-weighted respiratory triggered high spatial resolution images obtained in the hepatobiliary phase are technically feasible and significantly improve the image quality compared with breath-hold images.

Effect of butylscopolamine on image quality in MRI of the prostate

AIM To evaluate the impact of butylscopolamine on the quality of magnetic resonance imaging (MRI) images of the prostate. MATERIAL AND METHODS Eighty-two MRI examinations of the prostate were retrospectively analysed. MRI was performed with a combined endorectal/body phased-array coil including proton density-weighted (PD) sequence, T1-weighted turbo spin-echo (TSE)-sequence, and T2-weighted TSE-sequences. Forty milligrams of butylscopolamine was administered intramuscularly in 31 patients (im-group) and intravenously in 30 patients (iv-group). Twenty-one patients did not receive premedication with butylscopolamine (ø-group). Overall image quality, delineation of the bowel wall, and visualization of the prostate, neurovascular bundle, and pelvic lymph nodes were evaluated qualitatively using a five-point scale (from 1=excellent to 5=non-diagnostic/structure not discernible). Motion artefacts within the endorectal coil were quantified by baseline adjusted signal intensities inside the endorectal coil area. RESULTS Delineation of the bowel wall using the PD-sequence was significantly improved after both intramuscular and intravenous butylscopolamine administration (ø-group: 3.6+/-0.7; im-group: 2.9+/-0.7; iv-group: 2.9+/-0.7; p=0.001). However, there were no significant differences in motion artefacts measured within the endorectal coil (ø-group: 1.18+/-0.14; im-group: 1.15+/-0.11; iv-group: 1.12+/-0.06; p=0.39). There were also no significant differences in qualitative assessment of visualization of the prostate, neurovascular bundle, pelvic lymph nodes, and of overall image quality between the study groups. CONCLUSION : In conclusion, butylscopolamine had only a small effect on image quality and is not mandatory for MRI of the prostate.

DNA double-strand breaks as potential indicators for the biological effects of ionising radiation exposure from cardiac CT and conventional coronary angiography: a randomised, controlled study

AbstractObjectivesTo prospectively compare induced DNA double-strand breaks by cardiac computed tomography (CT) and conventional coronary angiography (CCA).Methods56 patients with suspected coronary artery disease were randomised to undergo either CCA or cardiac CT. DNA double-strand breaks were assessed in fluorescence microscopy of blood lymphocytes as indicators of the biological effects of radiation exposure. Radiation doses were estimated using dose–length product (DLP) and dose–area product (DAP) with conversion factors for CT and CCA, respectively.ResultsOn average there were 0.12 ± 0.06 induced double-strand breaks per lymphocyte for CT and 0.29 ± 0.18 for diagnostic CCA (P < 0.001). This relative biological effect of ionising radiation from CCA was 1.9 times higher (P < 0.001) than the effective dose estimated by conversion factors would have suggested. The correlation between the biological effects and the estimated radiation doses was excellent for CT (r = 0.951, P < 0.001) and moderate to good for CCA (r = 0.862, P < 0.001). One day after radiation, a complete repair of double-strand breaks to background levels was found in both groups.ConclusionsConversion factors may underestimate the relative biological effects of ionising radiation from CCA. DNA double-strand break assessment may provide a strategy for individualised assessments of radiation.Key Points• Radiation dose causes concern for both conventional coronary angiography and cardiac CT. • Estimations of the biological effects of ionising radiation may become feasible. • Fewer DNA double-strand breaks are induced by cardiac CT than CCA. • Conversion factors may underestimate the relative effects of ionising radiation from CCA.

Comparison of non-gated vs. electrocardiogram-gated 64-detector-row computed tomography for integrated electroanatomic mapping in patients undergoing pulmonary vein isolation

AIMS To compare non-gated vs. electrocardiogram (ECG)-gated 64-detector-row computed tomography (MDCT) of the left atrium (LA) for integrated electroanatomic mapping (EAM) in patients with paroxysmal atrial fibrillation (AF). METHODS AND RESULTS Twenty-nine consecutive patients with paroxysmal AF underwent MDCT prior to pulmonary vein isolation (PVI). All patients were in sinus rhythm both during CT imaging and PVI. Multi-detector-row computed tomography was performed in 15 patients without ECG-gating (non-gated MDCT) and in 14 patients with retrospective ECG-gating (ECG-gated MDCT). Image quality of LA reconstructions from MDCT was rated on a five-point scale (from 1 = excellent to 5 = segmentation failed). Registration error between LA geometry obtained from EAM and MDCT was calculated as the mean distance between EAM points and MDCT surface. In all patients, LA was successfully segmented from MDCT data. The segmentation process took 2:31 +/- 0:54 min for non-gated MDCT and 2:36 +/- 0:47 min for ECG-gated MDCT (P = 0.8). Image quality scores of LA reconstructions from non-gated and ECG-gated MDCT were 1.3 +/- 0.6 and 1.4 +/- 0.7, respectively (P = 0.76). There was no significant difference in the registration error between non-gated and ECG-gated MDCT (1.8 +/- 0.2 vs. 1.9 +/- 0.3 mm, respectively; P = 0.6). The radiation dose of non-gated MDCT was significantly lower compared with ECG-gated MDCT (4.6 +/- 1.4 vs. 13.4 +/- 3.6 mSv, respectively; P < 0.001). CONCLUSION Non-gated MDCT depicts LA with appropriate image quality for integrated EAM, while exposing patients to substantially lower radiation dose compared with ECG-gated MDCT.

High-resolution T2-weighted abdominal magnetic resonance imaging using respiratory triggering: impact of butylscopolamine on image quality.

Background: Respiratory triggering allows the acquisition of high-resolution magnetic resonance (MR) images of the upper abdomen. However, the depiction of organs close to the gastrointestinal tract can be considerably impaired by ghosting artifacts and blurring caused by bowel peristalsis. Purpose: To evaluate the effect of gastrointestinal motion suppression by intramuscular butylscopolamine administration on the image quality of a respiratory-triggered T2-weighted turbo spin-echo (T2w TSE) sequence of the upper abdomen. Material and Methods: Images of 46 patients were retrospectively analyzed. Twenty-four patients had received intramuscular injection of 40 mg butylscopolamine immediately before MR imaging. Fourteen of the 24 patients in the butylscopolamine group underwent repeat imaging after a mean of 29 min. Quantitative analysis of the ghosting artifacts was done by measuring signal intensities in regions of interest placed in air anterior to the patient. In addition, image quality was assessed qualitatively by two radiologists by consensus. Results: Spasmolytic medication with butylscopolamine reduced ghosting artifacts and significantly improved image quality of the respiratory-triggered T2w TSE sequence. The most pronounced effect of butylscopolamine administration on image quality was found for the pancreas and the left hepatic lobe. The rate of examinations with excellent or good depiction of the pancreas and the left hepatic lobe in the group without premedication and in the butylscopolamine group was 55% vs. 96% (pancreatic head), 35% vs. 88% (pancreatic body), 43% vs. 96% (pancreatic tail), and 45% vs. 83% (left hepatic lobe), respectively. Regarding the duration of the effect of intramuscular butylscopolamine, repeat imaging after a mean of 29 min did not result in a significant deterioration of image quality. Conclusion: Intramuscular butylscopolamine administration significantly improves image quality of respiratory-triggered T2-weighted abdominal MR imaging by persistent reduction of peristaltic artifacts. MR imaging of the liver and pancreas in particular benefits from the suppression of gastrointestinal peristalsis by butylscopolamine.

Evaluation of computed tomography in patients with atypical angina or chest pain clinically referred for invasive coronary angiography: randomised controlled trial

Objective To evaluate whether invasive coronary angiography or computed tomography (CT) should be performed in patients clinically referred for coronary angiography with an intermediate probability of coronary artery disease. Design Prospective randomised single centre trial. Setting University hospital in Germany. Participants 340 patients with suspected coronary artery disease and a clinical indication for coronary angiography on the basis of atypical angina or chest pain. Interventions 168 patients were randomised to CT and 172 to coronary angiography. After randomisation one patient declined CT and 10 patients declined coronary angiography, leaving 167 patients (88 women) and 162 patients (78 women) for analysis. Allocation could not be blinded, but blinded independent investigators assessed outcomes. Main outcome measure The primary outcome measure was major procedural complications within 48 hours of the last procedure related to CT or angiography. Results Cardiac CT reduced the need for coronary angiography from 100% to 14% (95% confidence interval 9% to 20%, P<0.001) and was associated with a significantly greater diagnostic yield from coronary angiography: 75% (53% to 90%) v 15% (10% to 22%), P<0.001. Major procedural complications were uncommon (0.3%) and similar across groups. Minor procedural complications were less common in the CT group than in the coronary angiography group: 3.6% (1% to 8%) v 10.5% (6% to 16%), P=0.014. CT shortened the median length of stay in the angiography group from 52.9 hours (interquartile range 49.5-76.4 hours) to 30.0 hours (3.5-77.3 hours, P<0.001). Overall median exposure to radiation was similar between the CT and angiography groups: 5.0 mSv (interquartile range 4.2-8.7 mSv) v 6.4 mSv (3.4-10.7 mSv), P=0.45. After a median follow-up of 3.3 years, major adverse cardiovascular events had occurred in seven of 167 patients in the CT group (4.2%) and six of 162 (3.7%) in the coronary angiography group (adjusted hazard ratio 0.90, 95% confidence interval 0.30 to 2.69, P=0.86). 79% of patients stated that they would prefer CT for subsequent testing. The study was conducted at a University hospital in Germany and thus the performance of CT may be different in routine clinical practice. The prevalence was lower than expected, resulting in an underpowered study for the predefined primary outcome. Conclusions CT increased the diagnostic yield and was a safe gatekeeper for coronary angiography with no increase in long term events. The length of stay was shortened by 22.9 hours with CT, and patients preferred non-invasive testing. Trial registration ClinicalTrials.gov NCT00844220.

Whole-heart coronary magnetic resonance angiography at 1.5 Tesla: does a blood-pool contrast agent improve diagnostic accuracy?

Objectives:To evaluate the impact of the blood-pool contrast agent gadofosveset trisodium on diagnostic accuracy of whole-heart coronary magnetic resonance angiography (CMRA) at 1.5 Tesla. Materials and Methods:Thirty consecutive patients with suspected coronary artery disease underwent free-breathing whole-heart CMRA at 1.5 Tesla. CMRA was performed with a T2-prepared steady-state free precession sequence (unenhanced CMRA) and an inversion-recovery-prepared steady-state free precession sequence after administration of gadofosveset trisodium (contrast-enhanced CMRA). Two readers independently performed a per-segment evaluation of CMRA (8 proximal and mid coronary segments) for detection of significant stenosis (≥50%) using invasive coronary angiography as reference. Disagreement was settled by consensus reading and interobserver variability was assessed using an unweighted kappa statistic. Results:Whole-heart CMRA was successfully performed in 27 patients. The percentage of assessable segments was significantly lower on unenhanced CMRA compared with contrast-enhanced CMRA (Reader 1: 79% [170/216] vs. 89% [192/216], respectively; Reader 2: 73% [157/216] vs. 87% [188/216], respectively; P < 0.001). Intention-to-diagnose analysis of the consensus reading yielded sensitivity, specificity, and diagnostic accuracy of unenhanced versus contrast-enhanced CMRA as follows: 73.1% versus 73.1% (P = 1.0), 68.3% versus 80.2% (P = 0.002), and 68.9% versus 79.3% (P = 0.004), respectively. The kappa value for interobserver agreement was 0.61 (95% confidence interval = 0.50–0.72) for unenhanced CMRA and 0.72 (95% confidence interval = 0.62–0.82) for contrast-enhanced CMRA. Conclusions:The blood-pool contrast agent gadofosveset trisodium increased the number of assessable coronary segments on whole-heart CMRA in comparison to unenhanced whole-heart CMRA. The impact of gadofosveset trisodium on diagnostic accuracy, however, was only minor.

Gadofosveset trisodium-enhanced magnetic resonance angiography of the left atrium—A feasibility study

AIM Imaging of the left atrium is regularly performed prior to pulmonary vein isolation. The aim of the study was to evaluate the feasibility of contrast-enhanced high-resolution magnetic resonance angiography (MRA) of the left atrium using the blood-pool contrast agent gadofosveset trisodium in comparison to noncontrast MRA. MATERIALS AND METHODS Twenty consecutive patients were examined by free-breathing electrocardiogram-gated whole-heart MRA (reconstructed spatial resolution, 0.7mm x 0.6mm x 0.8mm) with a noncontrast T2-prepared steady state free precession sequence (T2-prep SSFP) and a gadofosveset trisodium-enhanced inversion-recovery SSFP sequence (CE IR-SSFP). Contrast-to-noise ratio (CNR) of blood in the left atrium was determined. Depiction of the left atrium was rated by two radiologists in consensus. A cardiologist segmented the MR data sets and rated depiction of the left atrium. RESULTS Five of 20 patients had irregular breathing patterns with navigator efficiency less than 35% and were excluded from evaluation. CNR was significantly higher for CE IR-SSFP compared with T2-prep SSFP (18.4+/-5.3 vs. 11.7+/-3.5, p<0.01). Depiction of the left atrium by T2-prep SSFP was rated as good in four patients, moderate in ten patients, and poor in one patient, whereas depiction of the left atrium by CE IR-SSFP was rated as excellent in nine patients, good in four patients, and moderate in two patients. CE IR-SSFP allowed for semiautomated segmentation of the left atrium in 15 patients, whereas T2-prep SSFP allowed for segmentation only in ten patients. CONCLUSION Gadofosveset trisodium-enhanced MRA of the left atrium is feasible with significantly improved image quality compared to noncontrast MRA.