Gabriel Snoep

Selective Nodal Irradiation on Basis of 18FDG-PET Scans in Limited-Disease Small-Cell Lung Cancer: A Prospective Study

PURPOSE To evaluate the results of selective nodal irradiation on basis of (18)F-deoxyglucose positron emission tomography (PET) scans in patients with limited-disease small-cell lung cancer (LD-SCLC) on isolated nodal failure. METHODS AND MATERIALS A prospective study was performed of 60 patients with LD-SCLC. Radiotherapy was given to a dose of 45 Gy in twice-daily fractions of 1.5 Gy, concurrent with carboplatin and etoposide chemotherapy. Only the primary tumor and the mediastinal lymph nodes involved on the pretreatment PET scan were irradiated. A chest computed tomography (CT) scan was performed 3 months after radiotherapy completion and every 6 months thereafter. RESULTS A difference was seen in the involved nodal stations between the pretreatment (18)F-deoxyglucose PET scans and computed tomography scans in 30% of patients (95% confidence interval, 20-43%). Of the 60 patients, 39 (65%; 95% confidence interval [CI], 52-76%) developed a recurrence; 2 patients (3%, 95% CI, 1-11%) experienced isolated regional failure. The median actuarial overall survival was 19 months (95% CI, 17-21). The median actuarial progression-free survival was 14 months (95% CI, 12-16). 12% (95% CI, 6-22%) of patients experienced acute Grade 3 (Common Terminology Criteria for Adverse Events, version 3.0) esophagitis. CONCLUSION PET-based selective nodal irradiation for LD-SCLC resulted in a low rate of isolated nodal failures (3%), with a low percentage of acute esophagitis. These findings are in contrast to those from our prospective study of CT-based selective nodal irradiation, which resulted in an unexpectedly high percentage of isolated nodal failures (11%). Because of the low rate of isolated nodal failures and toxicity, we believe that our data support the use of PET-based SNI for LD-SCLC.

18FDG-PET based radiation planning of mediastinal lymph nodes in limited disease small cell lung cancer changes radiotherapy fields: A planning study

BACKGROUND AND PURPOSE To investigate the influence of selective irradiation of 18FDG-PET positive mediastinal nodes on radiation fields and normal tissue exposure in limited disease small cell lung cancer (LD-SCLC). MATERIAL AND METHODS Twenty-one patients with LD-SCLC, of whom both CT and PET images were available, were studied. For each patient, two three-dimensional conformal treatment plans were made with selective irradiation of involved lymph nodes, based on CT and on PET, respectively. Changes in treatment plans as well as dosimetric factors associated with lung and esophageal toxicity were analyzed and compared. RESULTS FDG-PET information changed the treatment field in 5 patients (24%). In 3 patients, this was due to a decrease and in 2 patients to an increase in the number of involved nodal areas. However, there were no significant differences in gross tumor volume (GTV), lung, and esophageal parameters between CT- and PET-based plans. CONCLUSIONS Incorporating FDG-PET information in radiotherapy planning for patients with LD-SCLC changed the treatment plan in 24% of patients compared to CT. Both increases and decreases of the GTV were observed, theoretically leading to the avoidance of geographical miss or a decrease of radiation exposure of normal tissues, respectively. Based on these findings, a phase II trial, evaluating PET-scan based selective nodal irradiation, is ongoing in our department.

Improved ejection fraction after exercise training in obesity is accompanied by reduced cardiac lipid content

CONTEXT Skeletal muscle and cardiac lipid accumulation are associated with diminished insulin sensitivity and cardiac function, respectively. In skeletal muscle, physical activity paradoxically increases fat accumulation, despite improvement in insulin sensitivity. Whether cardiac muscle responds similarly remains unknown. OBJECTIVE The objective of the study was to investigate cardiac lipid content and cardiac function after a 12-wk training program. DESIGN This was an intervention study with pre/postmeasurements. SETTING The study was conducted at Maastricht University Medical Center. PARTICIPANTS Participants included 14 healthy, male overweight/obese subjects (age 58.4 +/- 0.9 yr, body mass index 29.9 +/- 0.01 kg/m(2)). INTERVENTION Intervention included a supervised 12-wk training program with three sessions per week (endurance and strength training). MAIN OUTCOME MEASURES Maximal whole-body oxygen uptake, fasting plasma parameters, systolic function (by CINE-magnetic resonance imaging), and cardiac lipid content (by proton magnetic resonance spectroscopy) were measured. RESULTS Maximal whole-body oxygen uptake increased (from 2559 +/- 131 to 2702 +/- 124 ml/min after training, P = 0.05). Plasma concentrations of glucose decreased (from 6.3 +/- 0.2 to 5.7 +/- 0.2 mmol/liter, P < 0.001); plasma triacylglycerols and (free) fatty acids did not change. Also, body weight (from 94.2 +/- 3.6 to 92.9 +/- 3.6 kg, P = 0.10) and fat percentage (from 33.6 +/- 1.7 to 32.5 +/- 2.0%, P = 0.14) was unchanged. Left ventricular ejection fraction improved (from 52.2 +/- 1.3 to 54.2 +/- 1.2%, P = 0.02), and cardiac lipid content in the septum was decreased after training (0.99 +/- 0.15 to 0.54 +/- 0.04%, P = 0.02). CONCLUSIONS Twelve weeks of endurance/strength training significantly reduced cardiac lipid content in overweight subjects and was paralleled by improved ejection fraction. This is in line with a lipotoxic action of (excess) cardiac lipids on cardiac function, although a causal relationship cannot be derived from this study. Further research is needed to clarify the clinical relevance of cardiac lipid content in the etiology of cardiovascular complications.

Increase in left ventricular torsion‐to‐shortening ratio in children with valvular aortic stenosis

Perfusion of left ventricular (LV) subendocardium in valvular aortic stenosis (AS) patients is impaired. It was expected that this may lead to a reduction of subendocardial fiber contraction and, consequently, to an increase of LV torsion per amount of ejection. Using MR tagging (MRT), it was investigated whether the torsion‐to‐shortening ratio (TSR) is elevated in valvular AS patients. Six asymptomatic children with valvular AS were investigated using echo Doppler, ECG, exercise test, and MRT. LV torsion and natural strain of the inner diameter were determined from measured tag displacements in two short‐axis slices of the LV. In all AS patients TSR was ∼40% increased (0.62 ± 0.04 rad; mean ± SD) as compared to pediatric (0.44 ± 0.08 rad; n = 5) and adult controls (0.46 ± 0.08 rad; n = 9), indicating subendocardial contractile dysfunction. With other techniques hitherto used this type of dysfunction could not be detected. Magn Reson Med 51:135–139, 2004.

Follow-up with 18FDG-PET-CT after radical radiotherapy with or without chemotherapy allows the detection of potentially curable progressive disease in non-small cell lung cancer patients: a prospective study.

BACKGROUND Follow-up of patients treated with curative intent for non-small cell lung cancer (NSCLC) with X-ray or CT-scans is of unproven value. Furthermore, most patients with progressive disease present with symptoms outside of follow-up visits. Because the accuracy of (18)FDG-PET-CT is superior to CT, we hypothesised that FDG-PET-CT scans 3 months post-treatment could lead to early detection of progressive disease (PD) amenable for radical treatment. PATIENTS AND METHODS Hundred patients with NSCLC, treated with curative intent with (chemo) radiation, were prospectively evaluated. All patients underwent a planned FDG-PET-CT scan 3 months after the start of radiotherapy. RESULTS Twenty four patients had PD 3 months post-treatment. 16/24 patients were symptomatic. No curative treatment could be offered to any of these patients. In 3/8 asymptomatic patients progression, potentially amenable for radical therapy was found, which were all detected with PET, not with CT only. CONCLUSIONS PET-scanning after curative treatment for NSCLC led to the detection of progression potentially amenable for radical treatment in a small proportion (3%) of patients. Selectively offering a PET-CT scan to the patient group without symptoms could possibly lead to an effective follow-up method.

Tropical endomyocardial fibrosis (Davies' disease): case report demonstrating the role of magnetic resonance imaging.

Tropical endomyocardial fibrosis (TEMF), a restrictive cardiomyopathy of unclear etiology, is an endemic disease in equatorial Africa, South America and India. The patients are usually young, the onset of the disease and its clinical manifestations insidious, and the prognosis poor. We currently present a 50-year-old Congolese female who was referred with symptoms of progressive right-sided heart failure due to isolated TEMF of the right ventricle. Surgical resection of regional endomyocardial fibrosis was not possible and our patient was referred for cardiac transplantation. Cardiac magnetic resonance imaging (CMR) demonstrated the primary and secondary structural and functional abnormalities. CMR seems ideally suited to diagnose this condition and monitor response to medical and/or surgical therapy.

Detection of bone marrow metastases in small cell lung cancer. Comparison of magnetic resonance imaging with standard methods

In small cell lung cancer (SCLC), bone marrow metastases are frequently detected by bone scintigraphy (BS) and/or unilateral bone marrow biopsy and aspiration (BMBA). In this study, the value of magnetic resonance imaging (MRI) of thoracic spine and pelvis was compared with BS and BMBA and its clinical implication was evaluated in 42 patients with SCLC. Patients were staged (including BS, BMBA, CT thorax, Liver ECHO) as limited (LD) or extensive disease (ED) before and after MRI. MRI was positive in 12 BS negative (P = 0.003) and in 14 BMBA negative patients (P < 0.001), while in 8 patients, MRI was the only sign of ED, which resulted in a decrease of patients categorised with LD from 52 to 33%. However, in this small group of LD patients, there was no significant survival difference between LD (MRI pos) and LD (MRI neg) patients. It is concluded that MRI can be of value in the staging of LD patients, but it has no influence on survival.

Cardiac Sarcoidosis in a Patient With Hypertrophic Cardiomyopathy Demonstrated by Magnetic Resonance Imaging and Single Photon Emission Computed Tomography Dual-Isotope Scintigraphy

41-year-old man, who had been diagnosed with stage 2 pulmonary sarcoidosis 3 years earlier, was referred to the cardiac clinic complaining of palpitations, dyspnea, and atypical chest pain. Except for central obesity (body mass index of 37 kg/m 2 ) and hypertension, no abnormalities were found on physical examination. The 12-lead ECG demonstrated apical and inferolateral ST-segment elevation, whereas multiple polymorphic premature ventricular beats were found during exercise testing and 24-hour ambulatory ECG. Coronary angiography showed no abnormalities. Because of the man’s obesity, the image quality of the transthoracic echocardiography was suboptimal. Cardiac MRI revealed severe asymmetric hypertrophy of the left ventricle, a finding that points to hypertrophic cardiomyopathy. T2-weighted cardiac MRI revealed increased signal in the apical region (Figure 1), and contrast-enhanced cardiac MRI (0.1 mmol/kg gadolinium-diethylenetriamine pentaacetic acid [Gd-DTPA]) showed late enhancement of the same region (Figures 2 through 5). A dual-isotope 99m Tc-Hexamibi (Cardiolite, DuPont) and 111 In-pentetreotide (OctreoScan, Tyco Healthcare, Mallinckrodt Medical BV; dose 190 MBq) SPECT was performed during exercise (dose 280 MBq) and rest (dose 870 MBq), revealing a reversible apical perfusion defect and apical uptake of 111 Inpentetreotide (Figure 6). The presence of somatostatin receptors in the apical region suggests active apical cardiac sarcoidosis. The SPECT and cardiac MRI images were fused (Figures 7 and 8) by rigid-body transformations based on anatomic landmarks (apex and basal interventricular septum) and the geometric dimensions identified in the different types of images. The spatial image transformations were computed in the MatLab (MathWorks) programming environment. 111 Inpentetreotide binds to somatostatin receptors on macrophages and has been reported to be useful in the management of sarcoidosis. It is possible to differentiate between active inflammation and fibrosis with different cardiac MRI techniques (eg, T2-weighted versus contrast-enhanced T1weighted cardiac MRI). This case demonstrates the usefulness of matching different imaging techniques to visualize inflammation and the different stages of this process in the myocardium.

Imaging of Arrhythmogenic Right Ventricular Cardiomyopathy

Clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) remains challenging, especially in the early stages of the disease, and relies on Task Force criteria that encompass electrocardiographic, morphological (fibrofatty infiltration, wall thinning), and functional abnormalities (focal or global contraction abnormalities, right ventricle [RV] dilatation, and aneurysms).1 A 47-year-old male ARVC patient with a known plakophilin gene mutation and electrocardiographic signs of ARVC (T-wave inversion and epsilon waves in the right precordial leads, Figure, A, arrows) was scheduled for cardiac magnetic resonance and 64-slice cardiac computed tomographic imaging (MDCT) …

Quantification of transmural differences in myocardial function with MRI tagging

Many cardiac diseases cause transmural differences in myofiber function. With the Magnetic Resonance Imaging Tagging technique a grid of magnetic tags was attached to the heart. Using a model of cardiac mechanics the motion of these tags was analyzed to deduct the transmural gradient or myofiber shortening. In normal, young healthy subjects (n=9), the transmural difference in myofiber shortening varies little, about /spl plusmn/4% (sd) of mean shortening. In patients with aortic stenosis subendocardial function is at risk. In a group of such patients (n=5) fiber shortening in the subendocardial layers was found to be decreased by 23/spl plusmn/20% relative to the subepicardial layers. This finding indicates that a model of cardiac mechanics can be used as a tool to convert MRI-tagging motion data to clinically useful information on a transmural gradient in contractile function. Presently, no other methods are available to detect such transmural gradient noninvasively.