Radiochemotherapy with or without cetuximab for unresectable esophageal cancer: final results of a randomized phase 2 trial (LEOPARD-2).

PURPOSE: To investigate the efficacy and toxicity of cetuximab when added to radiochemotherapy for unresectable esophageal cancer. METHODS: This randomized phase 2 trial (clinicaltrials.gov, identifier NCT01787006) compared radiochemotherapy plus cetuximab (arm A) to radiochemotherapy (arm B) for unresectable esophageal cancer. Primary objective was 2­year overall survival (OS). Arm A was considered insufficiently active if 2­year OS was ≤40% (null hypothesis = H0), and promising if the lower limit of the 95% confidence interval was >45%. If that lower limit was >40%, H0 was rejected. Secondary objectives included progression-free survival (PFS), locoregional control (LC), metastases-free survival (MFS), response, and toxicity. The study was terminated early after 74 patients; 68 patients were evaluable. RESULTS: Two-year OS was 71% in arm A (95% CI: 55-87%) vs. 53% in arm B (95% CI: 36-71%); H0 was rejected. Median OS was 49.1 vs. 24.1 months (p = 0.147). Hazard ratio (HR) for death was 0.60 (95% CI: 0.30-1.21). At 2 years, PFS was 56% vs. 44%, LC 84% vs. 72%, and MFS 74% vs. 54%. HRs were 0.51 (0.25-1.04) for progression, 0.43 (0.13-1.40) for locoregional failure, and 0.43 (0.17-1.05) for distant metastasis. Overall response was 81% vs. 69% (p = 0.262). Twenty-six and 27 patients, respectively, experienced at least one toxicity grade ≥3 (p = 0.573). A significant difference was found for grade ≥3 allergic reactions (12.5% vs. 0%, p = 0.044). CONCLUSION: Given the limitations of this trial, radiochemotherapy plus cetuximab was feasible. There was a trend towards improved PFS and MFS. Larger studies are required to better define the role of cetuximab for unresectable esophageal cancer.

Time-resolved 3-dimensional magnetic resonance phase contrast imaging (4D Flow MRI) reveals altered blood flow patterns in the ascending aorta of patients with valve-sparing aortic root replacement.

OBJECTIVE: The aim of this study was to compare aortic flow patterns in patients after David valve-sparing aortic root replacement with physiologically shaped sinus prostheses or conventional tube grafts in healthy volunteers. METHODS: Twelve patients with sinus prostheses (55 ± 15 years), 6 patients with tube grafts (58 ± 12 years), 12 age-matched, healthy volunteers (55 ± 6 years), and 6 young, healthy volunteers (25 ± 3 years) were examined with time-resolved 3-dimensional magnetic resonance phase contrast imaging (4D Flow MRI). Primary and secondary helical, as well as vortical flow patterns, were evaluated. Aortic arch anatomy as a flow influencing factor was determined. RESULTS: Compared with volunteers, both sinus prostheses and tube grafts developed more than 4 times as many secondary flow patterns in the ascending aorta (sinus prostheses n = 1.6 ± 0.8; tube grafts n = 1.3 ± 0.6; age-matched, healthy volunteers n = 0.3 ± 0.5; young, healthy volunteers n = 0; P ≤ .012) associated with a kinking of the prosthesis itself or at its distal anastomosis. As opposed to round aortic arches in volunteers (n = 16/18), cubic or gothic-shaped arches predominated in patients (n = 16/18, P < .001). In all but 3 volunteers, 2 counter-rotating helices were confirmed in the ascending aorta and were defined as a primary flow pattern. This primary flow pattern did not develop in patients who underwent valve-sparing aortic root replacement. CONCLUSIONS: In patients after valve-sparing aortic root replacement, there was an increased number of secondary flow patterns in the ascending aorta. This seems to be related to surgically altered aortic geometry with kinking. Because flow alterations are known to affect wall shear stress, there seems to be an increased risk for vessel wall remodeling. Compared with previous 4D Flow MRI studies, primary flow patterns in the ascending aorta in healthy subjects were confirmed to be more complex. This underlines the importance of thorough examination of 4D Flow MRI data.

In-vivo treatment accuracy analysis of active motion-compensated liver SBRT through registration of plan dose to post-therapeutic MRI-morphologic alterations.

BACKGROUND/PURPOSE: In-vivo-accuracy analysis (IVA) of dose-delivery with active motion-management (gating/tracking) was performed based on registration of post-radiotherapeutic MRI-morphologic-alterations (MMA) to the corresponding dose-distributions of gantry-based/robotic SBRT-plans. METHODS: Forty targets in two patient cohorts were evaluated: (1) gantry-based SBRT (deep-inspiratory breath-hold-gating; GS) and (2) robotic SBRT (online fiducial-tracking; RS). The planning-CT was deformably registered to the first post-treatment contrast-enhanced T1-weighted MRI. An isodose-structure cropped to the liver (ISL) and corresponding to the contoured MMA was created. Structure and statistical analysis regarding volumes, surface-distance, conformity metrics and center-of-mass-differences (CoMD) was performed. RESULTS: Liver volume-reduction was -43.1 ±â€¯148.2 cc post-RS and -55.8 ±â€¯174.3 cc post-GS. The mean surface-distance between MMA and ISL was 2.3 ±â€¯0.8 mm (RS) and 2.8 ±â€¯1.1 mm (GS). ISL and MMA volumes diverged by 5.1 ±â€¯23.3 cc (RS) and 16.5 ±â€¯34.1 cc (GS); the median conformity index of both structures was 0.83 (RS) and 0.80 (GS). The average relative directional errors were ≤0.7 mm (RS) and ≤0.3 mm (GS); the median absolute 3D-CoMD was 3.8 mm (RS) and 4.2 mm (GS) without statistically significant differences between the two techniques. Factors influencing the IVA included GTV and PTV (p = 0.041 and p = 0.020). Four local relapses occurred without correlation to IVA. CONCLUSIONS: For the first time a method for IVA was presented, which can serve as a benchmarking-tool for other treatment techniques. Both techniques have shown median deviations <5 mm of planned dose and MMA. However, IVA also revealed treatments with errors ≥5 mm, suggesting a necessity for patient-specific safety-margins. Nevertheless, the treatment accuracy of well-performed active motion-compensated liver SBRT seems not to be a driving factor for local treatment failure.

Comparison of the Revenue Situation in Interventional Radiology Based on the Example of Peripheral Artery Disease in the Case of a DRG Payment System and Various Internal Treatment Charges.

PURPOSE: Calculation of process-orientated costs for inpatient endovascular treatment of peripheral artery disease (PAD) from an interventional radiology (IR) perspective. Comparison of revenue situations in consideration of different ways to calculate internal treatment charges (ITCs) and diagnosis-related groups (DRG) for an independent IR department. MATERIALS AND METHODS: Costs (personnel, operating, material, and indirect costs) for endovascular treatment of PAD patients in an inpatient setting were calculated on a full cost basis. These costs were compared to the revenue situation for IR for five different scenarios: 1) IR receives the total DRG amount. IR receives the following DRG shares using ITCs based on InEK shares for 2) "Radiology" cost center type, 3) "OP" cost center type, 4) "Radiology" and "OP" cost center type, and 5) based on DKG-NT (scale of charges of the German Hospital Society). RESULTS: 78 patients (mean age: 68.6 ±â€Š11.4y) with the following DRGs were evaluated: F59A (n = 6), F59B (n = 14), F59C (n = 20) and F59 D (n = 38). The length of stay for these DRG groups was 15.8 ±â€Š12.1, 9.4 ±â€Š7.8, 2.8 ±â€Š3.7 and 3.4 ±â€Š6.5 days Material costs represented the bulk of all costs, especially if new and complex endovascular procedures were performed. Revenues for neither InEK shares nor ITCs based on DKG-NT were high enough to cover material costs. Contribution margins for the five scenarios were 1 = €â€Š1,539.29, 2 = €â€Š-1,775.31, 3 = €â€Š-2,579.41, 4 = €â€Š-963.43, 5 = €â€Š-2,687.22 in F59A, 1 = €â€Š-792.67, 2 = €â€Š-2,685.00, 3 = €â€Š-2,600.81, 4 = €â€Š-1,618.94, 5 = €â€Š-3,060.03 in F59B, 1 = €â€Š-879.87, 2 = €â€Š-2,633.14, 3 = €â€Š-3,001.07, 4 = €â€Š-1,952.33, 5 = €â€Š-3,136.24 in F59C and 1 = €â€Š703.65, 2 = €â€Š-106.35, 3 = €â€Š-773.86, 4 = €â€Š205.14, 5 = €â€Š-647.22 in F59 D. InEK shares return on average €â€Š150 - 500 more than ITCs based on the DKG-NT catalog. CONCLUSION: In this study positive contribution margins were seen only if IR receives the complete DRG amount. InEK shares do not cover incurred costs, with material costs representing the main part of treatment costs. Internal treatment charges based on the DKG-NT catalog provide the worst cost coverage. KEY POINTS: · Internal treatment charges based on the DKG-NT catalog provide the worst cost coverage for interventional radiology at our university hospital.. · Shares from the InEK matrix such as the cost center "radiology" or "OP" as revenue for IR are not sufficient to cover incurred costs. A positive contribution margin is achieved only in the case of a compensation method in which IR receives the total DRG amount.. CITATION FORMAT: · Vogt FM, Hunold P, Haegele J et al. Comparison of the Revenue Situation in Interventional Radiology Based on the Example of Peripheral Artery Disease in the Case of a DRG Payment System and Various Internal Treatment Charges. Fortschr Röntgenstr 2017; 190: 348 - 357.

Direct dose correlation of MRI morphologic alterations of healthy liver tissue after robotic liver SBRT.

PURPOSE: For assessing healthy liver reactions after robotic SBRT (stereotactic body radiotherapy), we investigated early morphologic alterations on MRI (magnetic resonance imaging) with respect to patient and treatment plan parameters. PATIENTS AND METHODS: MRI data at 6-17 weeks post-treatment from 22 patients with 42 liver metastases were analyzed retrospectively. Median prescription dose was 40 Gy delivered in 3-5 fractions. T2- and T1-weighted MRI were registered to the treatment plan. Absolute doses were converted to EQD2 (Equivalent dose in 2Gy fractions) with α/ß-ratios of 2 and 3 Gy for healthy, and 8 Gy for modelling pre-damaged liver tissue. RESULTS: Sharply defined, centroid-shaped morphologic alterations were observed outside the high-dose volume surrounding the GTV. On T2-w MRI, hyperintensity at EQD2 isodoses of 113.3 ± 66.1 Gy2, 97.5 ± 54.7 Gy3, and 66.5 ± 32.0 Gy8 significantly depended on PTV dimension (p = 0.02) and healthy liver EQD2 (p = 0.05). On T1-w non-contrast MRI, hypointensity at EQD2 isodoses of 113.3 ± 49.3 Gy2, 97.4 ± 41.0 Gy3, and 65.7 ± 24.2 Gy8 significantly depended on prior chemotherapy (p = 0.01) and total liver volume (p = 0.05). On T1-w gadolinium-contrast delayed MRI, hypointensity at EQD2 isodoses of 90.6 ± 42.5 Gy2, 79.3 ± 35.3 Gy3, and 56.6 ± 20.9 Gy8 significantly depended on total (p = 0.04) and healthy (p = 0.01) liver EQD2. CONCLUSIONS: Early post-treatment changes in healthy liver tissue after robotic SBRT could spatially be correlated to respective isodoses. Median nominal doses of 10.1-11.3 Gy per fraction (EQD2 79-97 Gy3) induce characteristic morphologic alterations surrounding the lesions, potentially allowing for dosimetric in-vivo accuracy assessments. Comparison to other techniques and investigations of the short- and long-term clinical impact require further research.

Leakage of Hepaticojejunal Anastomosis: Radiological Interventional Therapy.

BACKGROUND: Hepaticojejunostomy is an established procedure accompanying liver resection as well as hepatobiliary and pancreatic surgery. Typical complications requiring radiological intervention are abscesses and anastomosis leakage. Biliary obstruction and strictures are less frequent indications for interventional radiology since many of them can be treated endoscopically. METHODS: Depending on anatomic location, underlying etiology, and complication of leakage, different procedures of interventional radiology are performed: treating abscesses through percutaneous abscess drainage (PAD), handling biliary leakage by percutaneous transhepatic biliary drainage (PTBD) after percutaneous transhepatic cholangiography (PTC), or rarely performed percutaneous stent implantation and internalization after PTC and PAD to treat biliary strictures or to cover the leak. A selective literature search was performed, taking into account recent papers of radiological interventions concerning leakage of hepaticojejunostomy. RESULTS: Different radiological interventions for the treatment of potentially devastating complications after hepaticojejunostomy are recommended. PAD and PTBD serve either as a definite treatment or as bridging therapy until re-surgery is performed. Complications mainly concern uncontrollable bleeding during the intervention. CONCLUSION: Radiological interventions are safe and usable if the indication is meticulously chosen. PAD is one of the most commonly performed procedures by interventional radiologists and a well-established and safe procedure. PTC, PTBD, and biliary stent implantation are important procedures which are required if endoscopic interventions failed or cannot be performed due to postoperatively changed anatomical structures.

Phase I Study of Definitive Radio-chemotherapy with Cisplatin, 5-Fluorouracil and Cetuximab for Unresectable Locally Advanced Esophageal Cancer.

BACKGROUND/AIM: Prognoses of patients receiving radio-chemotherapy with 5-fluorouracil (5-FU) and cisplatin for unresectable esophageal cancer may be improved with the addition of cetuximab. This phase I study aimed to define the maximum tolerated dose of 5-FU when combined with cisplatin, cetuximab and radiotherapy. PATIENTS AND METHODS: Treatment included 59.4 Gy of radiotherapy concurrently with two courses of cisplatin (20 mg/m2, d1-4) and 5-FU (dose level 0: 500 mg/m2, dose level 1: 750 mg/m2, d1-4; dose level 2: 1,000 mg/m2, d1-4), followed by two courses of chemotherapy. Cetuximab was given for 14 weeks (400 mg/m2 loading dose followed by 250 mg/m2 weekly). RESULTS: At dose level 1 (n=3) and 2 (n=3), no patient experienced a dose-limiting toxicity. Minor treatment modifications were due to organization or request by physicians/patients. At dose level 2, only five grade 3 adverse events occurred. CONCLUSION: Dose level 2 appears safe and is used in a subsequent randomized phase II study.

Treatment Planning Considerations for Robotic Guided Cardiac Radiosurgery for Atrial Fibrillation.

PURPOSE: Robotic guided stereotactic radiosurgery has recently been investigated for the treatment of atrial fibrillation (AF). Before moving into human treatments, multiple implications for treatment planning given a potential target tracking approach have to be considered. MATERIALS & METHODS: Theoretical AF radiosurgery treatment plans for twenty-four patients were generated for baseline comparison. Eighteen patients were investigated under ideal tracking conditions, twelve patients under regional dose rate (RDR = applied dose over a certain time window) optimized conditions (beam delivery sequence sorting according to regional beam targeting), four patients under ultrasound tracking conditions (beam block of the ultrasound probe) and four patients with temporary single fiducial tracking conditions (differential surrogate-to-target respiratory and cardiac motion). RESULTS: With currently known guidelines on dose limitations of critical structures, treatment planning for AF radiosurgery with 25 Gy under ideal tracking conditions with a 3 mm safety margin may only be feasible in less than 40% of the patients due to the unfavorable esophagus and bronchial tree location relative to the left atrial antrum (target area). Beam delivery sequence sorting showed a large increase in RDR coverage (% of voxels having a larger dose rate for a given time window) of 10.8-92.4% (median, 38.0%) for a 40-50 min time window, which may be significant for non-malignant targets. For ultrasound tracking, blocking beams through the ultrasound probe was found to have no visible impact on plan quality given previous optimal ultrasound window estimation for the planning CT. For fiducial tracking in the right atrial septum, the differential motion may reduce target coverage by up to -24.9% which could be reduced to a median of -0.8% (maximum, -12.0%) by using 4D dose optimization. The cardiac motion was also found to have an impact on the dose distribution, at the anterior left atrial wall; however, the results need to be verified. CONCLUSION: Robotic AF radiosurgery with 25 Gy may be feasible in a subgroup of patients under ideal tracking conditions. Ultrasound tracking was found to have the lowest impact on treatment planning and given its real-time imaging capability should be considered for AF robotic radiosurgery. Nevertheless, advanced treatment planning using RDR or 4D respiratory and cardiac dose optimization may be still advised despite using ideal tracking methods.

Time-resolved 3-dimensional magnetic resonance phase contrast imaging (4D Flow MRI) analysis of hemodynamics in valve-sparing aortic root repair with an anatomically shaped sinus prosthesis.

OBJECTIVE: The anatomically shaped sinus prosthesis (Uni-Graft W SINUS; Braun, Melsungen, Germany) used in valve-sparing aortic root replacement promises physiological hemodynamics believed to grant physiologic valve function. Using time-resolved 3-dimensional magnetic resonance phase contrast imaging (4D Flow MRI), we analyzed sinus vortex formation and transvalvular pressure gradients in patients with sinus prosthesis compared with age-matched and young healthy volunteers. METHODS: Twelve patients with sinus prosthesis (55 ± 15 years), 12 age-matched and 6 young healthy volunteers (55 ± 6 years, 25 ± 3 years, respectively) were examined at 3T with a 4D flow magnetic resonance imaging sequence. Sinus vortices visualized by streamlines and time-resolved particle paths were graded on a 4-point Likert scale. Time resolved pressure differences of the left ventricular outflow tract and the ascending aorta to a reference point in the aortic bulb as well as the transvalvular pressure gradient were evaluated. RESULTS: 4D flow visualizations revealed a propensity of the sinus prosthesis toward intermediate (50%) and large (28%) vortices compared with age-matched volunteers with small (61%) and intermediate (36%) vortices. Vortices in sinus prostheses had a similar configuration compared with those in volunteers. The peak transvalvular pressure gradient did not vary significantly between patients and age-matched volunteers (4.0 ± 0.9 mm Hg, 3.8 ± 0.7 mm Hg, P = .373), its temporal evolution resembled that of volunteers with a prolonged positive phase in patients. CONCLUSIONS: Hemodynamics closely relating to those of volunteers were confirmed in sinus prostheses, believed to grant physiological valve function. Minor differences are presumably attributed to graft compliance and temporal resolution of the acquisition. Nevertheless, long-term deterioration of valve function as it was described for straight grafts could potentially be decelerated using sinus prostheses.

Sudden hypertension in a kidney transplant recipient after a skiing accident.

INTRODUCTION: Complications after renal transplants are frequent. A well-known but less frequent complication is arteriovenous fistula formation, which can remain asymptomatic or present with hematuria, hypertension, or renal insufficiency. PRESENTATION OF CASE: We present the case of a young, male kidney transplant recipient with newly developed hypertension due to the formation of an arteriovenous fistula a long period after the last renal biopsy. DISCUSSION: In our case, the sonographic evaluation showed the aliasing phenomenon, which was useful in the detection of the AVF. Superselective transcatheter embolization is considered to be the treatment of choice in such cases and has been proven to be safe and effective, even in long-term evaluations. CONCLUSION: Our findings in this case highlight a rarely reported clinical presentation which physicians should be aware of when evaluating patients who have received a renal transplant.

Pulmonary vein isolation by radiosurgery: implications for non-invasive treatment of atrial fibrillation.

AIMS: Electrical isolation of the pulmonary veins (PVs) has been established in clinical routine as a curative treatment for atrial fibrillation (AF). While catheter ablation carries procedural risks, radiosurgery might be able to non-invasively induce lesions at the PV ostia to block veno-atrial electrical conduction. This porcine feasibility and dose escalation study determined the effect of radiosurgery on electrophysiologic properties of the left atrial-PV junction. METHODS AND RESULTS: Eight adult Goettingen mini-pigs underwent electrophysiological voltage mapping in the left atrium and the upper right PV. Radiation was delivered with a conventional linear accelerator. A single homogeneous dose ranging from 22.5 to 40 Gy was applied circumferentially to the target vein antrum. Six months after radiosurgery, electrophysiological mapping was repeated and a histological examination performed. Voltage mapping consistently showed electrical potentials in the upper right PV at baseline. Pacing the target vein prompted atrial excitation, thus proving veno-atrial electrical conduction. After 6 months, radiation had reduced PV electrogram amplitudes. This was dose dependent with a mean interaction effect of -5.8%/Gy. Complete block of atrio-venous electrical conduction occurred after 40 Gy dose application. Histology revealed transmural scarring of the targeted PV musculature with doses >30 Gy. After 40 Gy, it spanned the entire circumference in accordance with pulmonary vein isolation. CONCLUSION: Pulmonary vein isolation to treat AF can be achieved by radiosurgery with a conventional linear accelerator. Yet, it requires a high radiation dose which might limit clinical applicability.

Dose-escalation study for cardiac radiosurgery in a porcine model.

PURPOSE: To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. METHODS AND MATERIALS: Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm(3)). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. RESULTS: Transmural scarring of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. CONCLUSIONS: Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.

L1 cell adhesion molecule as a potential therapeutic target in murine models of endometriosis using a monoclonal antibody approach.

BACKGROUND/AIMS: The neural cell adhesion molecule L1CAM is a transmembrane glycoprotein abnormally expressed in tumors and previously associated with cell proliferation, adhesion and invasion, as well as neurite outgrowth in endometriosis. Being an attractive target molecule for antibody-based therapy, the present study assessed the ability of the monoclonal anti-L1 antibody (anti-L1 mAb) to impair the development of endometriotic lesions in vivo and endometriosis-associated nerve fiber growth. METHODS AND RESULTS: Endometriosis was experimentally induced in sexually mature B6C3F1 (n=34) and CD-1 nude (n=21) mice by autologous and heterologous transplantation, respectively, of endometrial fragments into the peritoneal cavity. Transplantation was confirmed four weeks post-surgery by in vivo magnetic resonance imaging and laparotomy, respectively. Mice were then intraperitoneally injected with anti-L1 mAb or an IgG isotype control antibody twice weekly, over a period of four weeks. Upon treatment completion, mice were sacrificed and endometrial implants were excised, measured and fixed. Endometriosis was histologically confirmed and L1CAM was detected by immunohistochemistry. Endometriotic lesion size was significantly reduced in anti-L1-treated B6C3F1 and CD-1 nude mice compared to mice treated with control antibody (P<0.05). Accordingly, a decreased number of PCNA positive epithelial and stromal cells was detected in autologously and heterologously induced endometriotic lesions exposed to anti-L1 mAb treatment. Anti-L1-treated mice also presented a diminished number of intraperitoneal adhesions at implantation sites compared with controls. Furthermore, a double-blind counting of anti-neurofilament L stained nerves revealed significantly reduced nerve density within peritoneal lesions in anti-L1 treated B6C3F1 mice (P=0.0039). CONCLUSIONS: Local anti-L1 mAb treatment suppressed endometriosis growth in B6C3F1 and CD-1 nude mice and exerted a potent anti-neurogenic effect on induced endometriotic lesions in vivo. The findings of this preliminary study in mice provide a strong basis for further testing in in vivo models.

Laryngeal chondrosarcoma with unusual dissemination to the humerus.

We report the case of an 81-year-old woman admitted to our clinic with a 16-month history of hoarseness due to unilateral vocal cord immobilization, slowly progressive dysphagia and an episode of painless swelling of the right arm. Radiological and histological workup revealed a medium-grade conventional chondrosarcoma of the cricoid cartilage with paratracheal spread and dissemination to the lung and the humeral bone. To our knowledge, this is the first humeral bone metastasis of laryngeal chondrosarcoma reported in the literature. The course of the presented case underlines the need for an early and detailed clinical and radiological workup of vocal cord immobilization.

Radiolabeled cetuximab plus whole-brain irradiation (WBI) for the treatment of brain metastases from non-small cell lung cancer (NSCLC).

BACKGROUND AND PURPOSE: The addition of systemic drugs to whole-brain irradiation has not improved the survival of patients with multiple brain metastases, most likely because the agents did not readily cross the blood-brain barrier (BBB). Radiolabeling of cetuximab was performed to investigate whether this antibody crosses the BBB. CASE REPORT: A patient with multiple brain lesions from non-small cell lung cancer was investigated. The largest metastasis (40 x 33 x 27 mm) was selected the reference lesion. On day 1, 200 mg/m(2) cetuximab (0.25% hot and 99.75% cold antibody) were given. On day 3, 200 mg/m(2) cetuximab (cold antibody) were given. Weekly doses of 250 mg/m(2) cetuximab were administered for 3 months. RESULTS: The reference lesion showed enhancement of radiolabeled cetuximab ((123)I-Erbi) on scintigraphy; (123)I-Erbi crossed the BBB and accumulated in the lesion. The reference lesion measured 31 x 22 x 21 mm at 4 months. Enhancement of contrast medium was less pronounced. CONCLUSION: This is the first demonstration of cetuximab crossing the BBB and accumulating in brain metastasis.

Left ventricular volumes and mass in marathon runners and their association with cardiovascular risk factors.

BACKGROUND: To assess left ventricular volumes and mass by cardiac magnetic resonance imaging in relation to conventional cardiovascular risk factors and coronary atherosclerotic plaque burden in master marathon runners aged > or =50 years. METHODS: Cardiac MRI was performed in 105 clinically healthy male marathon runners (mean age 57.3 +/- 5.7 years, range 50-71 years) on a 1.5 T MR system (Avanto, Siemens, Germany). Cine steady state free precession images in standard long and short axes views were acquired to assess left ventricular volumes and mass. Cardiovascular risk factors (blood pressure, HDL/LDL cholesterol, smoking, body mass index) were assessed and coronary artery calcification (CAC) was quantified by electron beam computed tomography. RESULTS: Left ventricular muscle mass (mean LVMM = 140 +/- 27 g; 73 +/- 13 g/m(2)) increased with increasing left ventricular end-diastolic volume (mean LVEDV = 137 +/- 32 ml; 72 +/- 15 ml/m(2)) (r = 0.41, P < 0.0001) and with systolic (r = 0.33, P = 0.005) and diastolic (r = 0.28, P = 0.005) blood pressures. Left ventricular EDV increased up to the age of 55 years, but decreased thereafter. Runners with LVMM > or =150 g had significantly higher CAC scores than runners with LVMM <150 g (median CAC score 110 vs. 25, P = 0.04). CONCLUSIONS: Increases in LVMM and LVEDV may not only represent a response to exercise but are dependent on age and blood pressure, also. In addition, a left ventricular hypertrophy without an increase in volume may be an indicator for early subclinical cardiac alterations in response to risk factor exposure.

Contrast-enhanced cardiac MRI before coronary artery bypass surgery: impact of myocardial scar extent on bypass flow.

The aim of the study was to relate the extent of myocardial late gadolinium enhancement (LGE) in cardiac MRI to intraoperative graft flow in patients undergoing coronary artery bypass graft (CABG) surgery. Thirty-three CAD patients underwent LGE MRI before surgery using an inversion-recovery GRE sequence (turboFLASH). Intraoperative graft flow in Doppler ultrasonography was compared with the scar extent in each coronary vessel territory. One hundred and fourteen grafts were established supplying 86 of the 99 vessel territories. A significant negative correlation was found between scar extent and graft flow (r = -0.4, p < 0.0001). Flow in grafts to territories with no or small subendocardial scar was significantly higher than in grafts to territories with broad nontransmural or transmural scar (75 +/- 39 vs. 38 +/- 26 cc min(-1); p < 0.0001). In summary, the extent of myocardial scar as defined by contrast-enhanced MRI predicts coronary bypass graft flow. Beyond the probability of functional recovery, preoperative MRI might add value to surgery planning by predicting midterm bypass graft patency.