The Metabolic Signature of Tumors as an Imaging Biomarker in Staging, Restaging and Therapy Response on FDG PET

Abstract

18 F FDG PET has been ever growing over the past decade. CMS reimbursements have followed an increase in the evidence of its utility and superior sensitivity to other morphological exams. This has been greatly aided by the National Oncologic PET Registry (NOPR), which allowed us to evaluate its impact on clinical management. Beyond the static notion of staging [1,2], FDG PET was shown in an NOPR report to change predicted clinical management in 33% of cases [3], not an insignificant number of patients whose therapeutic interventions would have been impacted, as well as an influence on cost saving and morbidity sparing strategies in cases where surgery was no longer an option. This effect was mostly due to a change in staging, by either down staging or upstaging patients. However, other clinical management tools can be extracted from medical imaging and guide the selection of the initial therapeutic approach as well as subsequent treatment modulation. Additional initial staging and restaging FDG PET indications are appropriately being added to the clinical arsenal physicians can use. Imaging in general and FDG PET more specifically could have a great value as an imaging biomarker. For example, the initial therapeutic approach could be impacted by the cancer specific Metabolic Signature (MS) of tumors beyond the notion of simple staging. Tumors of apparent similar histology and staging but different MS as defined by a quantitative FDG measure (SUV, total lesion glycolysis or other) may have a different prognosis and may require a different clinical management. FDG has been shown to correlate with Ki67 a marker of tumor proliferation and tumor aggressiveness [4-6]. The value of FDG PET imaging in this instance is that it can assess this parameter not only in the biopsied lesion but may give us some insight on the global and specific tumor burden of individual lesions within the same patient. It should be noted that tumors have been shown to often exhibit heterogeneity of at least molecular expression but also grade, proliferation and differentiation between the primary lesion and its metastasis. We have also described an aspect of this paradigm in an esophageal cancer patient where the HER2 molecular expression was absent in a metastatic liver lesion that responded to treatment but was present in the primary tumor that did not respond [7]. We can see this concept extrapolated to many tumors and readout sessions whether in the initial staging or follow-up phases of treatment. Another frequent occurrence with PET imaging nowadays is the flare up of granulomatous disease seen in the post-chemotherapy phase. We see this on a regular basis in nodal stations, the lungs and even the bone marrow and should not be misread as progression [8]. Although this can be seen with any cancer, it is especially true in lymphoma patients where these findings may be more problematic to interpret. The metabolic signature of tumors can also add some insight into the decision of whether low-grade follicular lymphoma patients should be treated. The current paradigm is not to treat low volume or asymptomatic patients. However if the MS of an individual patient was high, could that be evidence enough of a possible therapeutic benefit. Or if an upward change in MS is noted on serial surveillance FDG PET scans, would that be evidence enough of a transformation and therefore encourage re-biopsy and treatment.