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Once-daily oral AZD2171 at doses of 45 mg or less was generally well tolerated and was associated with encouraging antitumor activity in patients with a broad range of advanced solid tumors.

Positron emission tomography used to evaluate the uptake of FDG in tumors yields data that correlate with the antitumor effect of chemotherapy in patients with liver metastases from colorectal cancer.

These data support further investigation of T1 -weighted OE-MRI to identify regional tumor hypoxia. The quantification of AUCOE has translational potential as a clinical biomarker of hypoxia.

This paper discusses the effect of blood perfusion on the ablation of rat liver tissue with high-intensity focused ultrasound (HIFU). For this study a practical method has been developed, in which the liver blood flow can be reduced by ligation of the hepatic artery and portal vein. During the treatment the rat liver was mobilized out of the abdomen and the blood flow was measured using both the radioactive microsphere method and a laser Doppler blood-flow monitor. The results show that the hepatic blood flow was about 23 ml/100 g min-1 via the hepatic artery and about 227 ml/100 g min-1 via the portal vein. The total liver blood flow was reduced by 98% when both the hepatic artery and portal vein were ligated. Comparative lesions were made on the same liver lobes of rats with both normal and reduced blood flow using a focused ultrasound beam of 1.7 MHz, 67-425 W cm-2 spatially averaged focal intensity ISAL and 2-20 s exposure duration. A marked difference has been found between the lesion dimensions obtained with normal blood flow and that with reduced blood flow. For exposures at 169 W cm-2 the lesion diameter with normal blood flow was reduced by 14% for 3 s exposure duration compared to that obtained with both hepatic artery and portal vein ligated, while the reduction was more than 20% for longer durations.

ObjectivesTo assess the utility of diffusion weighted imaging for monitoring early treatment effects associated with a VEGF inhibitor.Materials and methodsTwenty-nine patients with metastatic abdominal and pelvic tumours were recruited and imaged with DW-MRI: twice at baseline, and after 7 and 28 days of treatment with cediranib. Tumour measures were derived using mono-exponential, bi-exponential and stretched-exponential models, and parameter repeatability and treatment effects seen after 7 and 28 days were assessed. Correlations with volume changes and DCE-MRI metrics were also assessed.ResultsDiffusion coefficient repeatabilities from all models were < 6 %; f and D* (bi-exponential) were 22 % and 44 %; α (stretched-exponential) was 4.2 %. Significant increases in the diffusion coefficients from all models were observed at day 28 but not day 7. Significant decreases in D* and f.D* were observed at day 7 and in f at day 28; significant increases in α were observed at both time-points. Weak correlations between DW-MRI changes and volume changes and DCE-MRI changes were observed.ConclusionDW-MRI is sensitive to early and late treatment changes caused by a VEGF inhibitor using non-mono-exponential models. Evidence of over-fitting using the bi-exponential model suggests that the stretched-exponential model is best suited to monitor such changes.Key points• Non-mono-exponential diffusion models widen sensitivity to a broader class of tissue properties.• A stretched-exponential model robustly detects changes after 7 days of VEGF-inhibitor treatment.• There are very weak correlations between DWI-IVIM perfusion and similar DCE-MRI measures.• Diffusion-weighted MRI is a highly informative technique for assessing novel tumour therapies.

PurposeChanges in tumour 3′-deoxy-3′-[18F]fluorothymidine (FLT) uptake during concurrent chemo-radiotherapy in patients with non-small cell lung cancer (NSCLC) have been reported, at variable time points, in two pilot positron emission tomography (PET) studies. The aim of this study was to assess whether FLT changes occur early in response to radiotherapy (RT) without concurrent chemotherapy and whether such changes exceed test-retest variability.MethodsSixteen patients with NSCLC, scheduled to have radical RT, underwent FLT PET once/twice at baseline to assess reproducibility and/or after 5–11 RT fractions to evaluate response. Primary and nodal malignant lesions were manually delineated on CT and volume, mean and maximum standardized uptake values (SUVmean and SUVmax) estimated. Analysis included descriptive statistics and parameter fitting to a mixed-effects model accounting for patients having different numbers of evaluable lesions.ResultsIn all, 35 FLT PET scans from 7 patients with a total of 18 lesions and 12 patients with a total of 30 lesions were evaluated for reproducibility and response, respectively. SUVmean reproducibility in primary tumours (SD 8.9 %) was better than SUVmax reproducibility (SD 12.6 %). In nodes, SUVmean and SUVmax reproducibilities (SD 18.0 and 17.2 %) were comparable but worse than for primary tumours. After 5–11 RT fractions, primary tumour SUVmean decreased significantly by 25 % (p = 0.0001) in the absence of significant volumetric change, whereas metastatic nodes decreased in volume by 31 % (p = 0.020) with a larger SUVmean decrease of 40 % (p < 0.0001). Similar changes were found for SUVmax.ConclusionAcross this group of NSCLC patients, RT induced an early, significant decrease in lesion FLT uptake exceeding test-retest variability. This effect is variable between patients, appears distinct between primary and metastatic nodal lesions, and in primary tumours is lower than previously reported for concurrent chemo-RT at a similar time point. These results confirm the potential for FLT PET to report early on radiation response and to enhance the clinical development of novel drug-radiation combinations by providing an interpretable, early pharmacodynamic end point.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-013-2632-3) contains supplementary material, which is available to authorized users.

The purpose of the study was to perform phantom studies to assess the impact of computed tomography (CT) system variability on quantitative measurements of contrast enhancement. A phantom containing tubes of contrast material at dilutions of 120, 1:35, 1:50, 1:100 and 1:200 arranged in air or water was imaged using 11 CT systems at 9 institutions. All systems had undergone routine calibration against air and water in accordance with the manufacturers' recommendations. For a given tube voltage, the relationship between the iodine concentration and CT attenuation value on a single system varied by 17 to 24% over 46-48 weeks. The coefficients of variance for iodine calibration factors across different CT systems were 8.9% in air and 5.1% in water. Calibration of individual CT systems for iodine response is required to allow comparison of quantitative measurements of contrast enhancement across different institutions. Using the iodine calibration factor to express contrast enhancement as iodine concentration would facilitate the universal application of diagnostic enhancement thresholds, especially if the necessary calculations were performed by software installed on the CT console.