Position PaperMeasurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations
Introduction
[18F]-Fluorodeoxyglucose ([18F]-FDG), a glucose analogue, demonstrates enhanced uptake in the majority of malignant tumours due to increased transport and fixation as [18F]-FDG-6-phosphate by hexokinase 1, 2, 3, 4. [18F]-FDG-6-phosphate is effectively ‘trapped’ as it is not a substrate for the subsequent enzymatically driven pathways for glucose and the rate of dephosphorylation is slow (Figure 1). The enhanced uptake is used for diagnosis, staging and detection of residual/recurrent cancer within diagnostic nuclear medicine. Increased tumour [18F]-FDG uptake as measured by positron emission tomography (PET), although a function of proliferative activity 5, 6, is also broadly related to viable tumour cell number 7, 8. If [18F]-FDG uptake is representative of tumour cell viability, then reduction in [18F]-FDG uptake with effective tumour therapy should reflect the tumour cell killing rate. A number of small clinical trials have indicated that quantification of changes in [18F]-FDG uptake may provide an early and sensitive pharmacodynamic marker of the tumoricidal effect of antiproliferative chemotherapy drugs. [18F]-FDG PET may have a role in improved monitoring of tumour response to anticancer drugs at a clinical and subclinical level as previously described by the European Organization for Research and Treatment of Cancer (EORTC) PET study group [9]. This may provide better and earlier assessment of chemotherapy drug efficacy in clinical trials and patient management. The methods of measurement of [18F]-FDG uptake are, however, currently diverse and timing with respect to chemotherapy variable.
The EORTC PET study group held a consensus meeting in February 1998 to review the current status of the technique. This was updated at a meeting during the EORTC strategy meeting in March 1999. The group were able to make initial recommendations for a common measurement standard and criteria for reporting alterations in [18F]-FDG uptake to assess clinical and subclinical response. These recommendations, based on presently available data, are not intended to have implications for regulatory authorities but rather to provide a common framework for data comparison. These recommendations will be subject to review on a three yearly cycle as these data mature. The group emphasised the multidisplinary nature of measuring and interpreting [18F]-FDG tumour uptake and actively encourages the full participation of the oncologist.
Section snippets
Materials and methods
A number of methods have been used to assess tumour [18F]-FDG uptake (Table 1) and can be divided into two categories: (i) assessment of [18F]-FDG accumulated at the time of measurement using visual interpretation and semiquantitative indices; and (ii) assessment of the rate of [18F]-FDG uptake over the measurement time using a kinetic approach.
Review of clinical studies
Reduction in [18F]-FDG uptake with effective chemotherapy may provide an early marker of response at a clinical and subclinical level. Figure 2 is a hypothetical illustration of how alterations in [18F]-FDG uptake may be related to clinical outcome. An assessment of changes in tumour [18F]-FDG uptake with chemotherapy was undertaken through review of published papers, including those of members of the EORTC PET study group, and discussion at the February 1998 meeting. The current imaging
Patient preparation
Attention to patient preparation improves the quality of [18F]-FDG imaging of tumours. The recommendations of the EORTC PET study group were:
- 1.
Patients should be fasted for oncology studies in order to enhance and standardise tumour [18F]-FDG uptake. For scans performed in the morning, overnight fasting is recommended. For studies performed in the afternoon, a light breakfast followed by a 6-h fast is recommended. Circulating glucose levels should be measured prior to administration of [18F]-FDG
Conclusions
Monitoring tumour response with [18F]-FDG PET is in its infancy. There is a requirement for larger-scale trials together with collection of reproducibility data, to assess the technique in relation to other methods of response assessment and clinical end-points. The EORTC PET study group has proposed a common method of assessing tumour [18F]-FDG uptake and reporting of response data. This is not intended to be exclusive of other measurements, but to provide a framework for comparison between
Acknowledgements
The authors would like to acknowledge the present and past members of the EORTC PET study group who have contributed to the current knowledge base on monitoring tumour response using [18F]-FDG PET. The EORTC PET study group is supported by a grant from the EORTC.
Professor Eremin, Aberdeen, U.K.; Dr L. Balkay, Debrecan, Hungary; Professor R. Bares, Tubingen; Professor R. Baum, Bad Berka, Germany; Dr M. Bergstrom, Uppsala, Sweden; Dr J.A.K. Blokland, Leiden, The Netherlands; Dr U. Cremerius,
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