PET Scanning: Worth the Cost in Cancer? Not for All Cancers-It’s Not Reliable Enough Yet
In order for a test to be reliable, it must be reproducible and minimize test-retest variability. Yet, as with many imaging tests, FDG-PET has variance in standard uptake value (SUV) calculations, and even if standardization could be achieved, there is the issue of treatment effects, which introduce additional complexities.
Positron emission tomography (PET) imaging is often used in the staging and follow-up of a variety of malignancies, including lymphoma, lung,[1-3] breast,[4] colon,[5] esophageal, gastric,[6] pancreatic, biliary, and gynecologic[7] cancers. For example, a quick search of the PubMed MeSH Database for the key words “positron emission tomography” and “pancreas” returns 140 citations. While there are benefits to 18-fluorodeoxyglucose PET (FDG-PET) imaging in some of these tumors, pancreatic ductal adenocarcinoma (PDAC) can be taken as a fairly typical example of a tumor in which both the strengths and weaknesses of PET are evident. At our center, using FDG-PET to identify the primary PDAC or to differentiate focal pancreatitis from PDAC has been problematic. The trouble lies in the frequent inability of PET to reliably identify early PDAC,[8] which would portend a good prognosis. While recent work has shown the value of FDG-PET in identifying metastatic disease, its weakness in identifying nearby metastatic lymph nodes has also been shown, supporting our experience.[9] A recent meta-analysis of FDG-PET in PDAC[10] that comprised 30 studies and 1,582 subjects showed the failure of FDG-PET as a tool for local staging.
In order for a test to be reliable, it must be reproducible and minimize test-retest variability. Yet, as with many imaging tests, FDG-PET has variance in standard uptake value (SUV) calculations,[11,12] as shown by a recent study of the use of FDG-PET at a single institution.[13] It should be noted, however, that some centers are studying methods that may reduce variability, such as semiautomatic PET analysis[14] or automated FDG dose administration.[15]
Yet even if standardization could be achieved, there is the issue of treatment effects, which introduce additional complexities. For example, after a patient receives neoadjuvant chemoradiation for locally advanced PDAC, the inflammation from radiation can be difficult, if not impossible, to distinguish from malignancy. Semiautomatic techniques may help to show results similar to those found in small samples of subjects in whom malignancy was distinguishable from radiation changes.[16] Of course, histopathology is not held to such a standard either, since monitoring response to therapy via biopsy is not performed.
In settings where FDG-PET as currently used has limitations, and where biopsy is not an option, perhaps the solution is to develop and utilize targeted molecular agents. Glycolysis may be too nonspecific to be a useful biomarker. Instead, a focus on agents such as [18F]-fluoro-azomycinarabino-furanoside ([18F]FAZA), which may be a biomarker of hypoxia and which has been studied in human subjects, may prove fruitful.[17] Preclinical and clinical targeted molecular imaging agents-such as integrin αvβ6,[18] carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6),[19] or human sodium iodide symporter gene (hNIS)[20]-are also under study as targets in pancreatic cancer imaging. As such molecular imaging agents and drugs become targeted to specific malignancies or to markers derived from an individual patient’s cancer, the nonspecific nature of FDG-PET imaging may be able to be avoided.
Financial Disclosure:The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.
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