A Phase II Study of the Central European Society of Anticancer-Drug Research (CESAR) Group: Results of an Open-Label Study of Gemcitabine plus Cisplatin with or without Concomitant or Sequential Gefitinib in Patients with Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium.

INTRODUCTION: This phase II trial evaluated the efficacy and safety of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib, in combination with first-line chemotherapy in advanced urothelial cancer. METHODS: Chemotherapy-naïve patients with advanced or metastatic urothelial carcinoma were randomized 1:1:1 to receive six cycles of chemotherapy (gemcitabine 1,250 mg/m2 on days 1 and 8, and cisplatin 70 mg/m2 on day 1 of every cycle) concomitantly with gefitinib 250 mg/day (arm A); or with sequential gefitinib (arm B); or alone (arm C). The primary endpoint was the time to progression (TTP). RESULTS: A total of 105 patients received study treatment. Median TTP for arms A, B, and C were 6.1, 6.3, and 7.8 months, respectively. There were no significant differences between treatment arms for any outcomes measured. The most common adverse events were nausea and vomiting. CONCLUSION: Gefitinib in combination with chemotherapy did not improve efficacy in advanced urothelial cancer.

Impact and safety of adjuvant chemotherapy on pulmonary function in early stage non-small cell lung cancer.

BACKGROUND: Pulmonary function may decline after induction chemotherapy and predict perioperative complications in non-small cell lung cancer (NSCLC). The influence of adjuvant chemotherapy is largely indeterminate. OBJECTIVE: To assess whether adjuvant chemotherapy alters pulmonary function and impacts on treatment-related adverse events. METHODS: In a trial on adjuvant chemotherapy (the TREAT trial), 132 patients with R0-resected NSCLC were randomised to 4 cycles of cisplatin-vinorelbine (CVb, n = 65) or cisplatin-pemetrexed (CPx, n = 67). Pulmonary function tests (forced expiratory volume in 1 s, FEV1, forced vital capacity, FVC, total lung capacity, TLC, diffusing capacity for carbon monoxide, DLCO, and blood gas analyses, BGA) were analysed before and 30 days after the last chemotherapy, and changes were calculated (Δ = mean differences). RESULTS: Overall, FVC increased significantly (Δ +290 ml, n = 76; p < 0.0001), while TLC did not change (Δ +220 ml, n = 41; p = 0.174). For CPx, FEV1 increased significantly (Δ +150 ml, n = 47; p = 0.0017), but not for CVb (Δ +30 ml, n = 30). DLCO decreased only for CVb (-8%, n = 6) but not for CPx (-0.39%, n = 17; p = 0.58). BGA did not change (p = 0.99). In a Cox regression analysis, baseline pulmonary function did not influence treatment failure. CONCLUSIONS: Adjuvant chemotherapy seems not to result in a decrease of pulmonary function parameters. A significant FVC increase was probably due to ongoing postoperative improvement. Decline of DLCO was noted with CVb but not with CPx. Pulmonary function does not impact on treatment failure.

Multicenter randomized open-label phase III study comparing efficacy, safety, and tolerability of conventional carboplatin plus etoposide versus dose-intensified carboplatin plus etoposide plus lenograstim in small-cell lung cancer in "extensive disease" stage.

BACKGROUND: The combination of carboplatin and etoposide (CE) is one of the most effective regimens in the treatment of small-cell lung cancer (SCLC). The aim of this study was to investigate whether dose-intensified CE with the supplementation of granulocyte-colony-stimulating factor (G-CSF) is more effective than conventional CE in terms of survival with acceptable toxicity. METHODS: In a 2-arm multicentric prospective open label study, adult patients with SCLC in "extensive disease" stage were randomized either to conventional CE (carboplatin AUC 5 on day 1 IV and etoposide 140 mg/m IV on days 1-3, q28 days) or to dose-intensified therapy (carboplatin AUC 5 on day 1 IV and etoposide 190 mg/m days 1-3 IV with lenograstim 263 microg subcutaneously on days 4-13, q21 days). Primary end point was overall survival; secondary endpoints were toxicity, quality of life, and disease-free survival. RESULTS: Seventy-nine patients were included. Thirty-seven received conventional CE and 42 received the dose-intensified regimen. Median survival in the conventional group and the dose-intensified group were 11.2 months [confidence interval (CI) 9.1-15.2] and 11.7 months (CI 8.8-14.7), respectively. Progression-free survival was 6.7 (CI 5.8-7.5) and 7.4 months (CI 6.2-9.0), respectively. There was no statistically significant difference between these groups. Grade 3/4 neutropenia occurred in 69.4% in the conventional arm versus 37.5% in the dose-intensified group (P = 0.009). CONCLUSION: Dose-intense CE with GM-CSF support can be administered safely but does not prolong overall or progression-free survival compared with standard therapy.

Computed tomography, positron emission tomography, positron emission tomography/computed tomography, and magnetic resonance imaging for staging of limited pleural mesothelioma: initial results.

OBJECTIVE: To evaluate and compare the role of computed tomography (CT), positron emission tomography (PET), PET/CT, and magnetic resonance imaging (MRI) in the correct staging of patients with limited malignant pleural mesothelioma (MPM). MATERIALS AND METHODS: Fifty-four patients with an epithelial MPM (34 men and 20 women) were included in this study. Patients were referred to our department for staging in a predicted resectable state (stage II/III). Within 3 days, PET/CT and MRI was performed in all patients. Images were evaluated by 3 specialists in the field of PET/CT and MRI. The subexaminations of PET/CT, PET, and CT were independently evaluated with respect to tumor stage. Subexaminations were compared with each other, with MRI and PET/CT. N-stage was verified by mediastinoscopy. Afterward, consensus reading was performed.In 52 patients, surgery served as gold standard. In 2 patients, follow-up control served as gold standard as an inoperable situation with distant metastases was found. Additionally, interobserver variability (kappa value) was calculated. RESULTS: In stage II, accuracy was 0.77 (CT), 0.86 (PET), 0.8 (MRI), 1.0 (PET/CT), and in stage III 0.75, 0.83, 0.9, 1.0. PET/CT was significantly more accurate (P < 0.05) in stages II and III compared with all other techniques. CT and MRI were not able to detect distant metastases in 2 patients, which changed therapy (operable vs. inoperable). Interobserver variability was 0.7, 0.9, 0.8, 1.0 in stage II and 0.9, 0.9, 0.9, 1.0 in stage III. CONCLUSION: PET/CT makes it possible to stage patients with limited MPM with high accuracy and low interobserver variability.

Therapy response in malignant pleural mesothelioma-role of MRI using RECIST, modified RECIST and volumetric approaches in comparison with CT.

To evaluate and compare early therapy response according to RECIST (response evaluation criteria in solid tumours) and modified RECIST criteria using MRI techniques in patients with malignant pleural mesothelioma (MPM) in comparison with CT. Fifty patients with MPM (32 male/18 female) were included in this study. Early therapy response was evaluated after 9 weeks [three of six chemotherapy (CHT)] cycles. Additionally patients were examined before chemotherapy, 4 weeks after early therapy response evaluation and after six cycles to evaluate diagnostic follow-up. RECIST and modified RECIST criteria were applied using CT and MRI (HASTE, VIBE, T2-TSE sequences). In MRI additionally a volumetric approach measuring tumour weight (overall segmented tumour volume) was applied. Additionally vital capacity (VC) was measured for correlation. Image interpretation was performed by three independent readers independently and in consensus. The 'gold standard' was follow-up examination. Twenty-eight patients showed partial response, 12 patients stable disease and 10 patients progressive disease at early therapy response evaluation. In the follow-up these results remained. For MRI, in 46 cases patients were identically classified using RECIST and modified RECIST criteria. Modified RECIST criteria were identically classified as gold standards in all cases, whereas using RECIST criteria in four cases there was a mismatch (partial response vs. stable disease). Modified RECIST kappa values showed better interobserver variability compared with RECIST criteria (kappa=0.9-1.0 vs. 0.7-1.0). For CT, in 44 cases patients were identically classified using RECIST and modified RECIST criteria. Modified RECIST criteria were identically classified as in gold standards in 48 out of 50 patients, whereas using RECIST criteria in 6 cases there was a mismatch (partial response vs. stable disease). Modified RECIST kappa values showed better interobserver variability compared with RECIST criteria (kappa=0.9-1.0 vs. 0.6-1.0). Modified RECIST criteria especially in combination with high-resolution MRI is a very accurate and reproducible technique to correctly evaluate early therapy response in MPM.

Immunotherapy of prostate cancer in a murine model using a novel GnRH based vaccine candidate.

Previous studies with gonadotrophin releasing hormone (GnRH/LHRH) vaccines have shown the usefulness of immunization against this hormone in prostate cancer. To this end, we have generated a completely synthetic peptide modified at position 6 and attached to the 830-844 tetanic toxoid (TT) helper T cell sequence. Through this work we have demonstrated that the GnRHm1-TT molecule was highly immunogenic when it is formulated as an oil-based emulsion adjuvated with Montanide ISA 51. That results correlated directly with testosterone reduction and tumor growth inhibition of the Dunning R3327-H androgen responsive prostate tumor model in rats. GnRHm1-TT, proved to be safe and useful for future clinical trials.

Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study.

PURPOSE: In postmenopausal women with estrogen receptor-positive early breast cancer, surgery is usually followed by a 5-year course of tamoxifen. This report presents results of a prospective, open-label, randomized study, designed to evaluate the benefits of switching to anastrozole after 2 years of tamoxifen treatment, compared with continuing on tamoxifen for 5 years. PATIENTS AND METHODS: After receiving tamoxifen treatment for 2 years, eligible patients (n = 979) were randomly assigned to switch to anastrozole (1 mg/d) or continue tamoxifen (20 or 30 mg/d) for an additional 3 years. Patients were monitored every 6 months during years 1 to 3 and annually thereafter. The primary efficacy variable was disease-free survival, including local or distant recurrence, new contralateral breast cancer, or death. Secondary variables were overall survival and assessment of safety. RESULTS: Switching to anastrozole resulted in a significant reduction in the risk of disease recurrence (hazard ratio [HR], 0.66; 95% CI, 0.44 to 1.00; P = .049), and improved overall survival (HR, 0.53; 95% CI, 0.28 to 0.99; P = .045) compared with continuing on tamoxifen. Fewer patients who switched to anastrozole reported serious adverse events (22.7% v 30.8%) compared with those who continued on tamoxifen, mainly due to more patients in the tamoxifen group with endometrial events. The overall safety profile for anastrozole was consistent with previous reports and no new safety issues were identified. CONCLUSION: Postmenopausal women who have taken tamoxifen for 2 years as adjuvant therapy are less likely to experience a recurrence of breast cancer and have improved overall survival if they switch to anastrozole compared with continuing to receive tamoxifen.

Effectiveness of switching from adjuvant tamoxifen to anastrozole in postmenopausal women with hormone-sensitive early-stage breast cancer: a meta-analysis.

BACKGROUND: For more than 20 years, tamoxifen has been the mainstay of adjuvant endocrine therapy for women with hormone-sensitive early-stage breast cancer. However, not only does tamoxifen have potential side-effects such as an increased risk of endometrial cancer and thromboembolic events, but patients can also develop resistance to the drug. We aimed to investigate whether switching treatment of postmenopausal women with such breast cancer to anastrozole after 2-3 years of tamoxifen would be more effective than continuing on tamoxifen for a total of 5 years. METHODS: We did a meta-analysis of three clinical trials--the Austrian Breast and Colorectal Cancer Study Group (ABCSG 8), Arimidex-Nolvadex (ARNO 95), and the Italian Tamoxifen Anastrozole (ITA) studies--in which postmenopausal women with histologically confirmed, hormone-sensitive early-stage breast cancer were randomised to 1 mg/day anastrozole (n=2009) after 2-3 years of tamoxifen treatment or to continued 20 or 30 mg/day tamoxifen (n=1997). We analysed the data with a stratified Cox proportional hazards model with the covariates of age, tumour size, nodal status, grade, surgery, and chemotherapy. FINDINGS: Patients who switched to anastrozole had fewer disease recurrences (92 vs 159) and deaths (66 vs 90) than did those who remained on tamoxifen, resulting in significant improvements in disease-free survival (hazard ratio 0.59 [95% CI 0.48-0.74]; p<0.0001), event-free survival (0.55 [0.42-0.71]; p<0.0001), distant recurrence-free survival (0.61 [0.45-0.83]; p=0.002), and overall survival (0.71 [0.52-0.98]; p=0.04). INTERPRETATION: Our results show that the clinical benefits in terms of event-free survival seen in individual trials for those patients who switched to anastrozole translate into a benefit in overall survival. These findings confirm that clinicians should consider switching postmenopausal women who have taken adjuvant tamoxifen for 2-3 years to anastrozole.

Contrast-enhanced 3D MRI of lung perfusion in children with cystic fibrosis--initial results.

This paper is a feasibility study of magnetic resonance imaging (MRI) of lung perfusion in children with cystic fibrosis (CF) using contrast-enhanced 3D MRI. Correlation assessment of perfusion changes with structural abnormalities. Eleven CF patients (9 f, 2 m; median age 16 years) were examined at 1.5 T. Morphology: HASTE coronal, transversal (TR/TE/alpha/ST: 600 ms/28 ms/180 degrees /6 mm), breath-hold 18 s. Perfusion: Time-resolved 3D GRE pulse sequence (FLASH, TE/TR/alpha: 0.8/1.9 ms/40 degrees ), parallel imaging (GRAPPA, PAT 2). Twenty-five data sets were acquired after intravenous injection of 0.1 mmol/kg body weight of gadodiamide, 3-5 ml/s. A total of 198 lung segments were analyzed by two radiologists in consensus and scored for morphological and perfusion changes. Statistical analysis was performed by Mantel-Haenszel chi-square test. Results showed that perfusion defects were observed in all patients and present in 80% of upper, and 39% of lower lobes. Normal lung parenchyma showed homogeneous perfusion (86%, P<0.0001). Severe morphological changes led to perfusion defects (97%, P<0.0001). Segments with moderate morphological changes showed normal (53%) or impaired perfusion (47%). In conclusion, pulmonary perfusion is easy to judge in segments with normal parenchyma or severe changes. In moderately damaged segments, MRI of lung perfusion may help to better assess actual functional impairment. Contrast-enhanced 3D MRI of lung perfusion has the potential for early vascular functional assessment and therapy control in CF patients.

Differential effects of CLDR and PDR brachytherapy on cell cycle progression in a syngeneic rat prostate tumour model.

PURPOSE: The study consisted of two treatment arms comparing the effects of CLDR (continuous low dose rate) and PDR (pulsed dose rate) brachytherapy on cell cycle progression in a radioresistant rat prostate tumour model. MATERIALS AND METHODS: Interstitial PDR and CLDR brachytherapy (both 192-Ir, 0.75 Gy/h) were administered to Dunning prostate R3327-AT1 carcinomas transplanted subcutaneously into the thigh of Copenhagen rats. Increasing doses of up to 20 as well as up to 40 Gy were applied. Cell cycle distributions of the aneuploid tumour cell subpopulations were determined at 4 h (3 Gy), 24 h (18 Gy), 48 h (20 and 36 Gy), as well as during the subsequent redistribution period (20 and 40 Gy) at 72, 96, and 120 h. Tumours either implemented with an empty tubing system (n=5) or under undisturbed growth (n=5) served as controls. Three animals were irradiated per time point and exposure condition. At least two flow cytometrical analyses were carried out per animal. RESULTS: The aneuploid cells possessed a constant DNA-Index of 1.9+/-0.06. In contrast to sham-treated controls, the aneuploid cell fraction with G2/M DNA content was significantly increased (p<0.05) after initiation of both, CLDR and PDR brachytherapy. However, CLDR resulted in an earlier accumulation of tumour cells in G2/M (24 h: 28% CLDR vs. 19% PDR, p<0.05) with a concomitant reduction of cells in G1, whereas PDR yielded delayed, but then more pronounced cell cycle changes, particularly expressed during the redistribution period after both 20 and 40 Gy. CONCLUSION: CLDR and PDR brachytherapy showed differential effects on cell cycle progression. The induction of a significantly earlier but also less persistent G2/M cell cycle arrest after CLDR compared to PDR brachytherapy implies that a substantially higher fraction of tumour cells are irradiated in G2/M after CLDR.

Assessment of reproducibility and stability of different breath-hold maneuvres by dynamic MRI: comparison between healthy adults and patients with pulmonary hypertension.

To assess the stability and reproducibility of different breath-hold levels in healthy volunteers and patients using dynamic MRI (dMRI). In ten healthy volunteers and ten patients with pulmonary hypertension (PH) and normal lung function craniocaudal intrathoracic distances (CCD) were measured during inspiratory and expiratory breath-hold (15 s) (in healthy volunteers additionally at a self-chosen mid-inspiratory breath-hold) using dMRI (trueFISP, three images/s). To evaluate stability and intraobserver reproducibility of the different breath-hold levels, CCDs, time-distance curves, confidence intervals (CIs), Mann-Witney U test and regression equations were calculated. In healthy volunteers there was a substantial decrease of the CCD during the inspiratory breath-hold in contrast to the expiratory breath-hold. The CI at inspiration was 2.84+/-1.28 in the right and 2.1+/-0.68 in the left hemithorax. At expiration the CI was 2.54+/-1.18 and 2.8+/-1.48. Patients were significantly less able to hold their breath at inspiration than controls (P<0.05). In patients CI was 4.53+/-4.06 and 3.46+/-2.21 at inspiration and 4.45+/-4.23 and 4.76+/-3.73 at expiration. Intraobserver variability showed no significant differences either in patients or in healthy subjects. Reproducibility was significantly lower at a self-chosen breath-hold level of the healthy volunteers. DMRI is able to differentiate stability and reproducibility of different breath-hold levels. Expiratory breath-hold proved to be more stable than inspiratory breath-hold in healthy volunteers and patients.

Focal gene induction in the liver of rats by a heat-inducible promoter using focused ultrasound hyperthermia: preliminary results.

OBJECTIVE: We sought to examine high-intensity focused ultrasound (HIFU)-induced hyperthermia in the liver of a rat model to focally induce green-fluorescent protein (GFP). MATERIALS AND METHODS: A total of 25 Copenhagen rats were included in this study. Rats were divided into groups treated with an adenovirus coding for green fluorescent protein (GFP) under the control of a hsp70B promoter and a CMV promoter. Ad-CMV-GFP-treated rats served as positive control. Untreated controls only subjected to MRI +/- HIFU-treatment served to find out optimal power of HIFU in the target area of the liver. Temperature was noninvasively monitored by temperature sensitive magnetic resonance imaging (MRI). RESULTS: Rats treated with Ad-hsp70B-GFP demonstrated localized gene induction within the liver parenchyma, in good correlation with MRI and histology. Applying an acoustic power of 1.92 W a relatively uniform focal temperature up to 42 +/- 5 degrees C within the liver parenchyma could be documented. 3 x 10(9) plaque-forming units proved to account for a very homogeneous liver infection. Number of fluorescent cells in the region of hyperthermia was similar to the control group treated with Ad-CMV-GFP. CONCLUSION: Using the introduced parameters spatially controlled gene induction within a parenchymal organ such as the liver in rats using HIFU under control of MRI is feasible.

External beam radiotherapy in the treatment of male breast carcinoma: patterns of failure in a single institute experience.

AIMS AND BACKGROUND: We analyzed our own results in the treatment of male breast cancer patients with respect to local control, overall survival and possible prognostic factors for local and distant control. METHODS: Thirty-one patients with 32 carcinomas of the male breast were treated with radiotherapy. Twenty-five patients received radiotherapy to the chest wall including or not regional lymphatics after initial mastectomy (n = 23) or after surgery for local recurrence (n = 2). Median total dose was 60 Gy to the chest wall and 46 Gy to regional lymphatics. Seven patients with metastatic disease were referred for palliative radiotherapy. RESULTS: Overall survival after postoperative radiotherapy was 40% after a median follow-up of 4.3 years. Actuarial 3-, 5- and 10-year survival was 82.6%, 56.5% and 43.5%, respectively. Five-year progression-free survival was 62.5%. Survival was significantly affected by the presence of lymph node metastases (P <0.001). Local recurrence was seen in one patient after 29 months. CONCLUSIONS: Postoperative radiotherapy is important in the management of male breast cancer to improve local control and progression-free survival, resulting in one local failure in our analysis. The presence of lymph node metastases significantly impairs survival.

Dynamic contrast-enhanced MRI for assessing the disease activity of multiple myeloma: a comparative study with histology and clinical markers.

PURPOSE: To examine whether parameters of dynamic, contrast-enhanced MRI (DCE MRI) reflect the degree of infiltration and vessel density in corresponding bone marrow biopsy specimens. MATERIALS AND METHODS: The pelvis of 24 patients with multiple myeloma (MM) was examined using contrast-enhanced DCE MRI. Biopsy was obtained from the spina iliaca posterior superior. Using a two-compartment model (assuming one intravascular and one interstitial compartment), the parameters amplitude (A, the maximum, relative signal increase over baseline) and the exchange rate constant (k(ep), describing the redistribution of contrast agent from the interstitial into the intravascular compartment) in the biopsied region were calculated and compared with the histological and clinical data. RESULTS: DCE MRI parameters were significantly higher in lesions with marked infiltration than with mild or no infiltration (P < 0.05). The amplitude normalized to that in the iliac artery (A(n)), but not k(ep), was higher in lesions with high vessel-density at histology (P = 0.01). Higher k(ep) levels were found in presence of increased serum immunoglobulins. CONCLUSION: Increased contrast uptake in the bone marrow of MM patients indicates at least moderate tumor involvement. Furthermore, the contrast enhancement correlates with vessel-density and serum markers of disease activity.

Influence of different breathing maneuvers on internal and external organ motion: use of fiducial markers in dynamic MRI.

PURPOSE: To investigate, with dynamic magnetic resonance imaging (dMRI) and a fiducial marker, the influence of different breathing maneuvers on internal organ and external chest wall motion. METHODS AND MATERIALS: Lung and chest wall motion of 16 healthy subjects (13 male, 3 female) were examined with real-time trueFISP (true fast imaging with steady-state precession) dMRI and a small inductively coupled marker coil on either the abdomen or thorax. Three different breathing maneuvers were performed (predominantly "abdominal breathing," "thoracic breathing," and unspecific "normal breathing"). The craniocaudal (CC), anteroposterior (AP), and mediolateral (ML) lung distances were correlated (linear regression coefficient) with marker coil position during forced and quiet breathing. RESULTS: Differences of the CC distance between maximum forced inspiration and expiration were significant between abdominal and thoracic breathing (p < 0.05). The correlation between CC distance and coil position was best for forced abdominal breathing and a marker coil in the abdominal position (r = 0.89 +/- 0.04); for AP and ML distance, forced thoracic breathing and a coil in the thoracic position was best (r = 0.84 +/- 0.03 and 0.82 +/- 0.03, respectively). In quiet breathing, a lower correlation was found. CONCLUSION: A fiducial marker coil external to the thorax in combination with dMRI is a new technique to yield quantitative information on the correlation of internal organ and external chest wall motion. Correlations are highly dependent on the breathing maneuver.

Improved vascular opacification in cerebral computed tomography angiography with 80 kVp.

PURPOSE: We sought to intraindividually compare computed tomography angiographies (CTAs) acquired at 80 kVp and 120 kVp with respect to vessel contrast, noise level, and radiation dose. MATERIAL AND METHODS: CTA was performed on a single-slice CT scanner using tube voltages of 80 kVp and 120 kVp in 29 patients with arteriovenous malformations. Mean Hounsfield Units (HU) were evaluated for different vessels and brain parenchyma. To determine contrast-to-noise ratios (CNRs), noise levels were estimated from phantom measurements. RESULTS: The calculated effective dose to male/female patients was 0.4/0.5 mSv for 80 kVp and 0.7/0.8 mSv for 120 kVp. CT density in blood vessels was between 297 and 458 HU for 80 kVp and 152 and 229 HU for 120 kVp (P<0.0001). Despite an increased noise level in the low-voltage images, the CNR was 26-59% higher at 80 kVp than at 120 kVp (P<0.05). CONCLUSION: The use of a reduced tube potential leads to improved CNR in CTA of the cerebral vasculature and a markedly reduced radiation exposure to patients.

Preoperative staging of renal cell carcinoma with inferior vena cava thrombus using multidetector CT and MRI: prospective study with histopathological correlation.

OBJECTIVE: To evaluate the accuracy of multidetector computed tomography (CT) and magnetic resonance imaging (MRI) in staging and estimating renal carcinomas with caval thrombus. METHODS: Initially, 23 patients with suspected caval thrombi were admitted into this prospective study. Triphasic CT imaging was performed using a multidetector CT with a reconstructed slice thickness of 2 mm. 3D CT reconstructions were used to improve surgical planning. MRI protocol included: a transversal T1-weighted GE sequence with and without Gd-DTPA, a transversal T2-weighted respiratory-gated TSE, and a coronal T1-weighted GE sequence with Gd-DTPA and fat saturation. In addition, a multiphase 3D angiography was performed after Gd-DTPA injection. Patients were divided into 3 groups: caval thrombus below the insertion of the hepatic veins, within the intrahepatic vena cava, and intra-atrial extension. The results the tumor thrombus extension and staging results of 2 independent readers were correlated with surgical and histopathological staging. RESULTS: Of the 23 patients admitted, CT and MR scans of 14/13 patients respectively were correlated with histopathological workup. CT thrombus detection sensitivity and specificity for both readers was 0.93 and 0.8 respectively. MRI sensitivity and specificity for both readers was 1.0/0.85 and 0.75. Readers I and II evaluated the uppermost extension of the cranial tumor thrombus by both CT and MRI. CT and MR accuracy was 78% and 72%, 88% and 76% respectively. CONCLUSION: In cases of a suspected tumor thrombus, MRI and multidetector CT imaging showed similar staging results. Consequently, these staging modalities can be used to assess the extension of the tumor thrombus.

Computer-assisted quantitative assessment of power Doppler US: effects of microbubble contrast agent in the differentiation of breast tumors.

RATIONALE AND OBJECTIVES: To objectively quantify the effects of a microbubble contrast agent to differentiate breast tumors with power doppler ultrasound and to compare these results with color doppler ultrasound (CD US). METHODS: In 47 patients a microbubble contrast agent was injected intravenously. Computer-assisted quantitative assessment of the color pixel density was performed to evaluate the increase in Doppler signals. Results were compared to previously published results of a color Doppler ultrasound study. RESULTS: Peak color pixel density at contrast-enhanced power Doppler ultrasound was higher for carcinomas than for benign tumors (P < 0.03). Time to peak enhancement was shorter in carcinomas than in benign tumors (P < 0.01). For both parameters, diagnostic accuracy of power Doppler ultrasound was 69 and 78%, and for color Doppler ultrasound 62 and 76%, respectively. CONCLUSIONS: Quantitative assessment of contrast-enhanced power Doppler ultrasound showed significant differences in malignant and benign breast tumors. Diagnostic accuracy of contrast-enhanced power Doppler ultrasound was higher compared to color Doppler ultrasound.

Measurement of tumor diameter-dependent mobility of lung tumors by dynamic MRI.

BACKGROUND AND PURPOSE: To assess the influence of tumor diameter on tumor mobility and motion of the tumor bearing hemithorax during the whole breathing cycle in patients with stage I non-small-cell lung cancer (NSCLC) using dynamic MRI. PATIENTS AND METHODS: Breathing cycles of thirty-nine patients with solitary NSCLCs were examined using a trueFISP sequence (three images per second). Patients were divided into three groups according to the maximal tumor diameter in the transverse plane (<3, 3-5 and >5 cm). Continuous time-distance curves and deep inspiratory and expiratory positions of the chest wall, the diaphragm and the tumor were measured in three planes. Motion of tumor-bearing and corresponding contralateral non-tumor bearing regions was compared. RESULTS: Patients with a tumor >3 cm showed a significantly lower diaphragmatic motion of the tumor bearing compared with the non-tumor bearing hemithorax in the craniocaudal (CC) directions (tumors 3-5 cm: 23.4+/-1.2 vs 21.1+/-1.5 cm (P<0.05); tumors >5 cm: 23.4+/-1.2 vs 20.1+/-1.6 cm (P<0.01). Tumors >5 cm in the lower lung region showed a significantly lower mobility compared with tumors <3 cm (1.8+/-1.0 vs 3.8+/-0.7 cm, P<0.01) in the CC directions. CONCLUSIONS: Dynamic MRI is a simple non-invasive method to differentiate mobility of tumors with different diameters and its influence on the surrounding tissue. Tumor diameter has a significant influence on tumor mobility and this might be taken into account in future radiotherapy planning.

Asbestos-related pleural disease: value of dedicated magnetic resonance imaging techniques.

OBJECTIVES: We sought to compare respiratory-gated high-spatial resolution magnetic resonance imaging (MRI) and radial MRI with ultra-short echo times with computed tomography (CT) in the diagnosis of asbestos-related pleural disease. METHODS: Twenty-one patients with confirmed long-term asbestos exposure were examined with a CT and a 1.5-T MR unit. High-resolution respiratory-gated T2w turbo-spin-echo (TSE), breath-hold T1w TSE, and contrast-enhanced fat-suppressed breath-hold T1w TSE images with an inplane resolution of less than 1 mm were acquired. To visualize pleural plaques with a short T2* time, a pulse sequence with radial k-space-sampling was used (TE = 0.5 milliseconds) before and after administration of Gd-DTPA. CT and MR images were assessed by 4 readers for the number and calcification of plaques, extension of pleural fibrosis, extrapleural fat, detection of mesothelioma and its infiltration into adjacent tissues, and detection of pleural effusion. Observer agreement was studied with the use of kappa statistics. RESULTS: The MRI protocol allowed for differentiation between normal pleura and pleura with plaques. Interobserver agreement was comparable for MRI and CT in detecting pleural plaques (median kappa = 0.72 for MRI and 0.73 for CT) and significantly higher with CT than with MRI for detection of plaque calcification (median kappa 0.86 for CT and 0.72 for MRI; P = 0.03). Median sensitivity of MRI was 88% for detection of plaque calcification compared with CT. For assessment of pleural thickening, pleural effusion, and extrapleural fat, interobserver agreement with MRI was significantly higher than with CT (median kappa 0.71 and 0.23 for pleural thickening, 0.87 and 0.62 for pleural effusion, and 0.7 and 0.56 for extrapleural fat, respectively; P < 0.05). For detection of mesothelioma, median kappa was 0.63 for MRI and 0.58 for CT. CONCLUSION: High-resolution MR sequences and radial MRI achieve a comparable interobserver agreement in detecting pleural plaques and even a higher interobserver agreement in assessing pleural thickening, pleural effusion, and extrapleural fat when compared with CT.