Monitoring Response to Therapeutic Interventions in Patients With Cancer

https://doi.org/10.1053/j.semnuclmed.2008.12.001Get rights and content

Positron emission tomography (PET) and PET/computed tomography (CT) with the glucose analog 18F-fluorodeoxyglucose (FDG) are increasingly used to assess response to therapy in patients, and there is converging evidence that changes in glucose utilization during therapy can be used to predict clinical outcome. Today, integrated PET/CT systems have mainly replaced stand-alone PET devices, providing the opportunity to integrate morphologic information and functional information. However, the use of PET/CT systems also gives rise to methodological challenges for the quantitative analysis of PET scans for treatment monitoring. Recently published single-center studies demonstrate that FDG-PET and FDG-PET/CT have been successfully used for monitoring of tumor response to cytotoxic therapy in a variety of tumor entities. The potential early identification of nonresponding tumors provides an opportunity to alter treatment regimens according to the individual chemosensitivity of the tumor tissue. In this article, we review the methodological background to monitoring of cancer treatment with PET/CT, the diagnostic and prognostic performance of PET/CT for predicting tumor response with the glucose analog FDG in various tumor entities, and the clinical potential of new imaging probes. In addition, the future direction of research and clinical applications is discussed.

Section snippets

Methodological Considerations

Therapy monitoring requires a high level of standardization and reproducibility of imaging because it aims to assess changes in tracer uptake during a period of weeks to months.5, 11 Additionally, imaging signals can only serve as a surrogate endpoint if the results correlate with clinical outcome and patient survival. In contrast to morphologic parameters, biologic imaging markers are subject to considerable inter- and intraindividual variability and thus are more susceptible to physiologic

Therapy Monitoring with 18F-FDG-PET/CT

Numerous clinical studies have evaluated the role of FDG-PET for assessment of early and late therapy response (Table 1, Table 2), tumor control, and prediction of prognosis. Especially the evaluation of response to therapy appears to be one of the most promising future indications for 18F-FDG-PET/CT imaging in clinical routine. The following section gives an overview of the role of 18F-FDG-PET/CT in the assessment of therapy response and prognosis, with special emphasis on early therapy

Therapy Monitoring with 18F-FLT-PET

PET with the use of the glucose analog FDG is an established imaging modality for predicting tumor response to therapy and patient survival.145 However, FDG is not tumor specific and can also accumulate in inflammatory lesions such as tuberculosis (granulomas), inflammation, and sarcoidosis, reducing its specificity and diagnostic accuracy.146, 147 For assessment of proliferative activity and better differentiation of inflammation from malignant tissue, measurement of tumor growth and DNA

Therapy Monitoring with Hypoxia Tracers

PET and PET/CT offer the possibility of in vivo mapping of regional tumor hypoxia with adequate anatomic resolution as well as monitoring of therapy through follow-up mapping of hypoxia. Derivatives of misonidazole—an azomycin-based hypoxic cell sensitizer that was introduced in radiation oncology decades ago—have been successfully labeled with positron emitters. FMISO is a radiopharmaceutical directly derived from misonidazole and is the most extensively studied PET agent for hypoxia mapping

Outlook

Despite the very promising results of recently published and ongoing trials evaluating the role of FDG-PET for response assessment, future validation of FDG-PET/CT for monitoring tumor response is mandatory. From our perspective, the following main aspects should be the focus of future research activities: (1) randomized multicenter trials and standardization of response assessment by PET and (2) assessment and evaluation of oncologic therapies employing new imaging probes.

The MUNICON trial was

Acknowledgments

We appreciate the excellent contributions made by our colleagues PD Dr. Andreas Buck, PD Dr. Ambros Beer, PD Dr. Hinrich Wieder, Dr. Michael Souvatzoglou, and Mrs. Christine Praus.

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