The study was undertaken in order to compare dose plans for intensity-modulated radiotherapy (IMRT) with 3D conformal radiotherapy (3D-CRT) dose plans in patients with nasopharyngeal carcinoma (NPC). Clinical data from 20 consecutive patients treated with IMRT are presented. For 11 patients 3D-CRT plans were made and compared to the IMRT plans with respect to doses to the planning target volumes (PTVs) and to organs at risk (OARs). For comparison of the conformation of dose to defined target volumes the conformity index (CI) was used. Target volume coverage and critical organ protection were significantly improved with IMRT compared to 3D-CRT. One-year loco-regional control, distant metastasis-free survival, and overall survival were 79%, 72%, and 80%. Two patients have had recurrence in the clinical target volume (CTV) only and seven patients have relapsed in distant organs and/or in head-and-neck areas outside the target areas. The study confirms that IMRT is superior to 3D-CRT in the treatment of NPC. As locoregional control of NPC improves we are facing an increasing number of recurrences outside the irradiated area.

PET allows non-invasive mapping of tumor hypoxia, but the combination of low resolution, slow tracer adduct-formation and slow clearance of unbound tracer remains problematic. Using a murine tumor with a hypoxic fraction within the clinical range and a tracer post-injection sampling time that results in clinically obtainable tumor-to-reference tissue activity ratios, we have analyzed to what extent inherent limitations actually compromise the validity of PET-generated hypoxia maps.Mice bearing SCCVII tumors were injected with the PET hypoxia-marker fluoroazomycin arabinoside (FAZA), and the immunologically detectable hypoxia marker, pimonidazole. Tumors and reference tissue (muscle, blood) were harvested 0.5, 2 and 4 h after FAZA administration. Tumors were analyzed for global (well counter) and regional (autoradiography) tracer distribution and compared to pimonidazole as visualized using immunofluorescence microscopy.Hypoxic fraction as measured by pimonidazole staining ranged from 0.09 to 0.32. FAZA tumor to reference tissue ratios were close to unity 0.5 h post-injection but reached values of 2 and 6 when tracer distribution time was prolonged to 2 and 4 h, respectively. A fine-scale pixel-by-pixel comparison of autoradiograms and immunofluorescence images revealed a clear spatial link between FAZA and pimonidazole-adduct signal intensities at 2 h and later. Furthermore, when using a pixel size that mimics the resolution in PET, an excellent correlation between pixel FAZA mean intensity and density of hypoxic cells was observed already at 2 h post-injection.Despite inherent weaknesses, PET-hypoxia imaging is able to generate quantitative tumor maps that accurately reflect the underlying microscopic reality (i.e., hypoxic cell density) in an animal model with a clinical realistic image contrast.

The aim of this study was to assess the value of fluorodeoxyglucose positron emission tomography (FDG PET) imaging of small pulmonary nodules incidentally detected by spiral computed tomography (CT) in a high-risk population. Ten patients (five females, five males, aged 54-72 years) were recruited from an ongoing 4-year placebo controlled intervention study of the effect of inhaled steroids in 300 smokers with moderate to severe chronic obstructive pulmonary disease. The participants received yearly CT scans of the chest. Patients with a negative chest radiograph at the time of inclusion, but with pulmonary nodules indeterminate for malignancy detected by conventional spiral CT on a subsequent scan, were referred for FDG PET. Histological diagnoses were sought for all nodules with FDG uptake or where CT showed that they had grown. Ten patients had pulmonary nodules indeterminate for malignancy (approx. 3.3% of the entire study population). The prevalence of malignancy in this group was 50%. The accuracy of PET was high, in spite of the fact that seven patients had nodules smaller than 15 mm and two patients had bronchoalveolar cell carcinoma. This small prospective study indicates that subsequent assessment with FDG PET of small pulmonary nodules incidentally detected by CT has the potential to minimize the numbers of invasive procedures performed in individuals with a benign pulmonary lesion. FDG PET also increases the possibility of an early diagnosis as compared to the strategy of watchful waiting.

Relapse occurs in 30% of patients with stage I non-seminomatous germ cell tumours (NSGCT) within 1 year after orchiectomy. Whole-body positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) may detect small metastases when standard staging with computed tomography (CT) and tumour markers is negative. In this study, 46 patients underwent FDG-PET after staging with normal CT and tumour markers. To exclude diagnostic test bias and workup bias, all patients had routine follow-up with repeated CT and tumour marker evaluation, even though the initial FDG-PET was positive. Thirty-six patients have remained disease free with a median follow-up of 48 months (range 24–76). Ten patients (22%) suffered disease relapse after a median of 2 months (range 1–8), and of these, seven had a true positive initial PET with increased uptake of FDG indicating metastatic disease. There were three false negative and no false positive PET scans. The sensitivity, specificity and accuracy of PET were 70%, 100% and 93%, respectively. The sensitivity of detecting small retroperitoneal metastases was 88%. The negative and positive predictive values were 92% and 100%, respectively, whereas the negative predictive value of standard staging procedures was 78%. FDG-PET thus seems to be superior to conventional staging (P=0.06) in stage I NSGCT. This non-invasive method may improve the overall management of patients with NSGCT.

OBJECTIVES:To demonstrate the efficacy of whole-body 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) in the detection of a carcinoma of unknown primary after conventional diagnostic workup in patients with a metastatic neck lesion and to demonstrate how the treatment policy of wide-field irradiation can be safely modified in relation to the findings from PET scanning.STUDY DESIGN:Prospective cohort study of consecutive patients.METHODS:Forty-two consecutive patients with squamous cell or undifferentiated metastatic disease in the neck from a carcinoma of unknown primary were enrolled after standard clinical workups. These patients underwent extensive clinical investigations including endoscopy under anesthesia with multiple mucosal biopsies and diagnostic imaging as well. If no primary site was indicated at this stage, a whole-body 18F-FDG PET scan was performed.RESULTS:Potential focal pathological uptake indicated a primary tumor in 20 of 42 cases (48%). After PET, this was confirmed by additional investigations in 10 patients (24%). Of these, seven primaries were found in the head and neck region (hypopharynx [three], base of tongue/vallecula [two], nasopharynx [1], floor of mouth [1]), and three primaries were found below the clavicles (lung [1], esophagus [1], and abdomen [1]. Positron emission tomography resulted in significant modifications of radiation treatment fields or fractionation prescriptions in all the patients who were diagnosed with a primary tumor after PET.CONCLUSION:With our present strategy of wide-field irradiation in patients with neck node metastases from a carcinoma of unknown primary, whole-body 18F-FDG PET had treatment-related implications in 24% (10 of 42) of the patients.

To evaluate whether electrical admittance of intracellular water is applicable for monitoring filling of the heart, we determined the difference in intracellular water in the thorax (Thorax(ICW)), measured as the reciprocal value of the electrical impedance for the thorax at 1.5 and 100 kHz during lower body negative pressure (LBNP) in humans. Changes in Thorax(ICW) were compared with positron emission tomography-determined C(15)O-labeled erythrocytes over the heart. During -40 mmHg LBNP, the blood volume of the heart decreased by 21 +/- 3% as the erythrocyte volume was reduced by 20 +/- 2% and the plasma volume declined by 26 +/- 2% (P < 0.01; n = 8). Over the heart region, LBNP was also associated with a decrease in the technetium-labeled erythrocyte activity by 26 +/- 4% and, conversely, an increase over the lower leg by 92 +/- 5% (P < 0.01; n = 6). For 15 subjects, LBNP increased thoracic impedance by 3.3 +/- 0.3 Omega (1.5 kHz) and 3.0 +/- 0.4 Omega (100 kHz), whereas leg impedance decreased by 9.0 +/- 3.3 Omega (1.5 kHz) and 6.1 +/- 3 Omega (100 kHz; P < 0.01). Thorax(ICW) was reduced by 7.1 +/- 1.9 S. 10(-4) (P < 0.01) and intracellular water in the leg tended to increase (from 37.8 +/- 4.6 to 40.9 +/- 5.0 S. 10(-4); P = 0.08). The correlation between Thorax(ICW) and heart erythrocyte volume was 0.84 (P < 0.05). The results suggest that thoracic electrical admittance of intracellular water can be applied to evaluate changes in blood volume of the heart during LBNP in humans.

We evaluated positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) in the detection of recurrent head and neck cancer, and compared visual and quantitative interpretation of PET images for their accuracy in the identification of tumour recurrence. Sixty-two FDG PET studies were performed in 56 patients having a total of 81 lesions, which were clinically suspected for recurrent carcinoma of the head and neck. The PET images were interpreted visually, and tracer uptake was quantitated as the standardised uptake value adjusted to body weight (SUV). Sensitivity of visual interpretation of the PET images for the presence of malignancy ranged from 84 to 95%, and specificity from 84 to 93%, respectively, depending on the selected scheme for grading of the lesions. Malignant lesions accumulated significantly more FDG than the benign ones (the median SUVs were 6.8 and 3.3, respectively, P<0.001). However, there was a wide overlap of the FDG uptake values between these two groups. Hence, the highest accuracy of quantitative analysis in correct identification of tumour recurrence (75% at Receiver Operating Curve analysis) was inferior to that of visual analysis (89%). FDG PET is feasible for the detection of recurrent head and neck cancer. Although quantitation of FDG uptake using SUV shows significantly higher tracer concentrations for malignant than benign lesions, the wide overlap of individual SUVs between these two groups is a serious concern in diagnostic evaluation. Therefore, in clinical practice it may be preferable to identify the presence of tumour recurrence within this patient group by qualitative interpretation of the PET images.

Purpose: To examine the value of PET in diagnosis and staging of suspected lung cancer.Methods: 20 (13 male; mean age: 56 yr., range: 22-83 yr.) patients with chest X-ray findings suspicious of malignancy were staged a) "clinically" (X-ray, history/physical examination, lung function), b) by chest CT of thorax/upper abdomen, and c) by whole-body PET (GE Advance, visual analysis). The CT and PET studies were performed within 2 weeks of admission and read blinded to all information except the chest X-ray report. The decision to refer to mediastinoscopy/thoracotomy was made by a tumor board using clinical information, CT and PET findings. In principle, suspected metastatic lesions were biopsied before surgery. The gold standard was histology from biopsy or thoracotomy, or resolution of the X-ray findings and symptoms.Results: One patient was excluded because of uncertain diagnosis. In 3 (15%) patients surgery was avoided mainly because of the PET findings. In one SCLC patient and one lymphoma patient, PET showed extensive disease, which changed the chemotherapy regime. Accuracy was 83% for clinical stage, 79% for CT and 77% for PET. Four (20%) false positive PET findings were caused by granuloma, pneumonia and BOOP. These nodules were only 1 to <3 cm, while malignant nodules were 2-8 cm. There were no false negative PET or CT studies.Conclusion: FDG-PET is valuable in patients suspected for pulmonary malignancy, since thoracotomy was avoided in 15% of patients and in 10% of patients more extensive disease was found which changed the chemotherapy regime.

The management of patients with unknown primary tumours (UPT) often includes a large number of radiographical studies and invasive procedures, but the occult primary tumour is detected in less than 25%. In this prospective study we explored whether non-invasive whole body PET scans using FDG (18-F-fluorodeoxyglucose) are of clinical value in detection of UPT. Whole-body FDG-PET scans were performed in 20 patients following standard staging procedures according to histology. PET results were verified either histologically or by the clinical course of the disease. 11 patients had neck metastases (5 squamous cell, 5 adenocarcinomas and 1 poorly differentiated carcinoma). The remaining patients had metastases located in bone (3), bone marrow (1), brain (1), pericardium (1), skin (1), pleura (1) and chest wall (1). All metastatic lesions were visible with PET. In 13 patients PET suggested the site for the primary tumour and this was verified in 9 (45%), either histologically or by the clinical course of disease. 8 of these had primary lung cancer and 1 had carcinoma at the basis of the tongue. In most patients PET had no treatment related implications. 3 patients with non-small cell lung cancer (NSCLC) received chemotherapy prompted by the PET result. The rest received either radical radiotherapy to the head and neck region (7), palliative radiotherapy to the metastatic lesion (8), chemotherapy based on signet ring cell carcinoma in bone marrow (1) or no therapy (1). These results indicates that PET is useful in UPT preceding expensive and invasive diagnostic procedures and can result in a faster diagnosis in approximately one third of the patients who then avoid unnecessary extensive procedures. Furthermore, a larger proportion of patients will receive treatment aimed at the correct diagnosis. A prospective cost-effectiveness analysis of PET in this setting is warranted.

Positron emission tomography (PET scanning) is a useful tool in staging of malignant melanoma. A radiolabelled glucoseanalogue can demonstrate changes in metabolism and thus identify malignancy in macroscopic unchanged structures. It is a non-invasive, fast method to identify especially visceral, still symptomless metastases. The patient can often be spared from mutilating surgery.