PET and Sarcoma
Treatment of malignant sarcomas in the last decade has emphasized the need for pre-operative neoadjuvant chemotherapy for high grade tumors despite reports of variable efficacy for this group of patients. Assessing the tumor grade or prognosis is often challenging due to sampling error and tissue heterogeneity in patients presenting with large tumors. Compared to the use of FDG PET imaging to diagnose, assess and stage other cancer histologies, this imaging technique is relatively under utilized in patients with sarcoma. Although sarcomas occur less frequently than many other histologies, their relative lack of response to treatment and the frequency of metastases at presentation make them excellent candidates as malignancies where molecular imaging techniques can make a contribution to better patient outcome. These imaging techniques can also be exploited to help identify newer possibly more effective therapy strategies, aimed at improving patient survival.
Published clinical imaging trial data from our group and others have shown that FDG PET imaging in sarcomas can make significant contributions to treatment planning, and study of the behaviors of the different sarcoma histologic subgroups. FDG is taken up into tissues according to their relative rate of tissue metabolism. Consequently, malignant regions within the tumor have higher metabolic rates than surrounding tissues, and these increased abnormal uptake regions are used to identify and characterize the probability of malignant behavior. PET images are high resolution, are always reformatted for analysis in three dimensional images, and the image uptake data can be used quantitatively or semi-quantitatively to determine tissue region specific uptake of an imaging agent (in clinical use, FDG). This imaging technique has been found to reliably discriminate low from high grade sarcomas. However, tumor FDG uptake values have ranges that are somewhat sub-type specific in soft tissue sarcomas (Ref. 1). Additionally, an FDG PET image of a mass suspicious for malignant behaviour on other imaging can direct the surgeon to the area most likely to yield diagnostic tissue on biopsy. Because of its direct relationship to tissue metabolism, the highest FDG uptake areas in a tumor reflect the most biologically aggressive areas.
New clinical studies continue to emerge on the utility of tumor FDG uptake as a biomarker for treatment response in many cancers, including sarcomas. The changes in tumor FDG uptake in a patient are very often seen in the absence of changes in tumor dimensions, rendering standard anatomic imaging measures of response less reliable for clinical trials requirements. Decreases in FDG uptake in sarcomas correlate with better survival, which validate its use as a tumor response biomarker. In our practice, in fact, anecdotally, we have seen increases in tumor size accompanied by significant decreases in tumor FDG uptake, suggesting that the tumor response process is multifactorial and may include processes that enlarge the tumor profile; such as edema or cystic fluid accumulation.
The time has come for FDG PET imaging to be accepted by the sarcoma community as an important contributor of patient specific information for treatment planning and assessment. Use of this technique will lead rapidly to the implementation of more biologically specific tracers for sarcoma biologic behaviour, where we will have the opportunity to probe tumors for factors acting to increase risk of treatment failure, or success. Soft tissue sarcoma patients with high grade tumors today have about a 60% overall 5 year survival rate from the time of diagnosis. We submit that consistent use of PET molecular imaging methods are key tools in characterizing and understanding sarcoma behaviour in clinical practice and clinical trials aimed at increasing patient survival.