Treatment Planning and Volumetric Response Assessment for Yttrium-90 Radioembolization: Semiautomated Determination of Liver Volume and Volume of Tumor Necrosis in Patients with Hepatic Malignancy

Purpose

The primary purpose of this study was to demonstrate intraobserver/interobserver reproducibility for novel semiautomated measurements of hepatic volume used for Yttrium-90 dose calculations as well as whole-liver and necrotic-liver (hypodense/nonenhancing) tumor volume after radioembolization. The secondary aim was to provide initial comparisons of tumor volumetric measurements with linear measurements, as defined by Response Evaluation Criteria in Solid Tumors criteria, and survival outcomes.

Methods

Between 2006 and 2009, 23 consecutive radioembolization procedures were performed for 14 cases of hepatocellular carcinoma and 9 cases of hepatic metastases. Baseline and follow-up computed tomography obtained 1?month after treatment were retrospectively analyzed. Three observers measured liver, whole-tumor, and tumor-necrosis volumes twice using semiautomated software.

Results

Good intraobserver/interobserver reproducibility was demonstrated (intraclass correlation [ICC]?>?0.9) for tumor and liver volumes. Semiautomated measurements of liver volumes were statistically similar to those obtained with manual tracing (ICC?=?0.868), but they required significantly less time to perform (p?<?0.0001, ICC?=?0.088). There was a positive association between change in linear tumor measurements and whole-tumor volume (p?<?0.0001). However, linear measurements did not correlate with volume of necrosis (p?>?0.05). Dose, change in tumor diameters, tumor volume, and necrotic volume did not correlate with survival (p?>?0.05 in all instances). However, Kaplan?CMeier curves suggest that a >10% increase in necrotic volume correlated with survival (p?=?0.0472).

Conclusion

Semiautomated volumetric analysis of liver, whole-tumor, and tumor-necrosis volume can be performed with good intraobserver/interobserver reproducibility. In this small retrospective study, measurements of tumor necrosis were suggested to correlate with survival.     

Characterization of chromosome 1 abnormalities in malignant melanomas

Chromosome 1 abnormalities are the most commonly detected aberrations in many cancers including malignant melanomas. Specific breakpoints are reported for malignant melanomas throughout the chromosome but especially at 1p36 and at several sites throughout 1p22-q21. In addition, partial deletions and loss of heterozygosity have been found on 1p indicating the possible location of tumor suppressor genes. Here we have characterized the involvement of chromosome 1 in a series of seven malignant melanoma cell lines. Initial chromosome painting studies revealed that six of the cell lines had chromosome 1 rearrangements. Deletions involving 1p10-32, 1q11-44, and 1q25-44 were observed. The other rearrangement breakpoints included three in the 1q10-p11 region with the rest at 1p36, 1p34, 1p32, 1p31, 1p12-13, 1q21, and 1q23. The breaks at 1q10-p11 were investigated further using an alpha-satellite 1 centromere probe and yeast artificial chromosomes (YACs) from the region. Two of the 1q10-p11 breaks mapped in the centromeric region, while the others mapped to variable sites. This suggests that the role of these rearrangements in the pathogenesis of melanomas does not involve the alteration of specific oncogenes in the breakpoint region. During the YAC mapping a previously undetected, small (<1 Mbp) del(1)(p10p11) was identified. This deletion lies within minimal overlapping deleted regions reported in head and neck as well as breast carcinomas and it could therefore facilitate the isolation of a carcinoma-associated tumor suppressor gene.     

Association between GAB2 haplotype and higher glucose metabolism in Alzheimer's disease-affected brain regions in cognitively normal APOEε4 carriers

In a genome-wide association study (GWAS) of late-onset Alzheimer's disease (AD), we found an association between common haplotypes of the GAB2 gene and AD risk in carriers of the apolipoprotein E (APOE) ε4 allele, the major late-onset AD susceptibility gene. We previously proposed the use of fluorodeoxyglucose positron emission tomography (FDG-PET) measurements as a quantitative pre-symptomatic endophenotype, more closely related to disease risk than the clinical syndrome itself, to help evaluate putative genetic and non-genetic modifiers of AD risk. In this study, we examined the relationship between the presence or absence of the relatively protective GAB2 haplotype and PET measurements of regional-to-whole brain FDG uptake in several AD-affected brain regions in 158 cognitively normal late-middle-aged APOEε4 homozygotes, heterozygotes, and non-carriers. GAB2 haplotypes were characterized using Affymetrix Genome-Wide Human SNP 6.0 Array data from each of these subjects. As predicted, the possibly protective GAB2 haplotype was associated with higher regional-to-whole brain FDG uptake in AD-affected brain regions in APOEε4 carriers. While additional studies are needed, this study supports the association between the possibly protective GAB2 haplotype and the risk of late-onset AD in APOEε4 carriers. It also supports the use of brain-imaging endophenotypes to help assess possible modifiers of AD risk.     

Cerebral perfusion and oxygenation differences in Alzheimer's disease risk

Functional MRI has demonstrated differences in response to memory performance based on risk for Alzheimer's disease (AD). The current study compared blood oxygen level dependent (BOLD) functional MRI response with arterial spin labeling (ASL) perfusion response during an associative encoding task and resting perfusion signal in different risk groups for AD. Thirteen individuals with a positive family history of AD and at least one copy of the apolipoprotien E epsilon4 (APOE4) gene (high risk) were compared to ten individuals without these risk factors (low risk). In the medial temporal lobes (MTLs) the high risk group had an elevated level of resting perfusion, and demonstrated decreased fractional BOLD and perfusion responses to the encoding task. However, there was no difference in the absolute cerebral blood flow during the task. These data demonstrate that individuals with increased risk for Alzheimer's disease have elevated MTL resting cerebral blood flow, which significantly influences apparent differences in BOLD activations. BOLD activations should be interpreted with caution, and do not necessarily reflect differences in neuronal activation.     

Application of selective extraction to the study of iron species present in diet and rat gastrointestinal tract contents.

Iron speciation in rodent diet and rat gastrointestinal tract lumen during dietary digestion and absorption was investigated with a novel selective extraction technique. Five Fe fractions were identified, namely exchangeable (soluble in 1 M-magnesium chloride), carbonate-bound (soluble in mild acid), oxide-bound (soluble in hydroxylamine-acetic acid), organic-bound (soluble after treatment with peroxide in nitric acid) and residual. Fe from the pelleted diet was mobilized by rat stomach to the exchangeable fraction, then redistributed to the carbonate- and oxide-bound fractions on passage through the proximal small intestine. In vitro incubation of diet with hydrochloric acid failed to mimic the in vivo effect of the stomach. In vitro neutralization of stomach contents with bicarbonate was found to produce a similar effect on Fe speciation to that seen when diet passed the proximal small intestine in vivo. Comparison of 59Fe speciation in extrinsically labelled diet with endogenous Fe speciation showed that extrinsic labelling does not uniformly label all endogenous species. The experiments suggest that selective extraction may provide a useful approach to the study of Fe species present in diets, in vitro digestions and gastrointestinal contents.