Elsevier

European Journal of Cancer

Volume 35, Issue 13, December 1999, Pages 1773-1782
European Journal of Cancer

Position Paper
Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations

https://doi.org/10.1016/S0959-8049(99)00229-4Get rights and content

Abstract

[18F]-fluorodeoxyglucose ([18F]-FDG) uptake is enhanced in most malignant tumours which in turn can be measured using positron emission tomography (PET). A number of small clinical trials have indicated that quantification of the change in tumour [18F]-FDG uptake may provide an early, sensitive, pharmacodynamic marker of the tumoricidal effect of anticancer drugs. This may allow for the introduction of subclinical response for anticancer drug evaluation in early clinical trials and improvements in patient management. For comparison of results from smaller clinical trials and larger-scale multicentre trials a consensus is desirable for: (i) common measurement criteria; and (ii) reporting of alterations in [18F]-FDG uptake with treatment. This paper summarises the current status of the technique and recommendations on the measurement of [18F]-FDG uptake for tumour response monitoring from a consensus meeting of the European Organization for Research and Treatment of Cancer (EORTC) PET study group held in Brussels in February 1998 and confirmed at a subsequent meeting in March 1999.

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,

References (51)

  • P. Price et al.

    Can positron emission tomography (PET) be used to detect subclinical response to cancer therapy? The EC PET Oncology Concerted Action and the EORTC PET study group

    Eur. J. Cancer.

    (1995)
  • J.M. Rozental et al.

    Early changes in tumour metabolism after treatmentthe effects of stereotactic radiotherapy

    Int. J. Radiat. Oncol. Biol. Phys.

    (1991)
  • K Herholz et al.

    FDG transport and phosphorylation in human gliomas measured with dynamic PET

    J. Neurooncol.

    (1992)
  • R.L. Wahl et al.

    Metabolic monitoring of breast cancer chemohormonotherapy using positron emission tomographyinitial evaluation

    J. Clin. Oncol.

    (1993)
  • R.S. Brown et al.

    Overexpression of Glut-1 glucose transporter in human breast cancer. An immunohistochemical study

    Cancer

    (1993)
  • R.S. Brown et al.

    Intratumoural distribution of tritiated-FDG in breast carcinomacorrelation with Glut-1 expression and FDG uptake

    J. Nucl. Med.

    (1996)
  • H. Minn et al.

    Fluorodeoxyglucose imaginga method to assess the proliferative activity of human cancer in vivo. Comparison with DNA flow cytometry in head and neck tumours

    Cancer

    (1988)
  • J. Okada et al.

    Positron emission tomography using fluorine-18-fluorodeoxyglucose in malignant lymphomaa comparison with proliferative activity

    J. Nucl. Med.

    (1992)
  • K. Higashi et al.

    Does FDG uptake measure proliferative activity of human cancer cells? In vitro comparison with DNA flow cytometry and tritiated thymidine uptake

    J. Nucl. Med.

    (1993)
  • K. Herholz et al.

    Correlation of glucose consumption and tumour cell density in astrocytomas. A stereotactic PET study

    J. Neurosurg.

    (1993)
  • H.Q. Woodward et al.

    Expression of tissue isotope distribution

    J. Nucl. Med.

    (1975)
  • K.R. Zasadny et al.

    Standardised uptake values of normal tissues at PET with 2-[fluorine-18]-fluoro-2-deoxy-d-glucosevariations with body weight and a method for correction

    Radiology

    (1993)
  • C.K. Kim et al.

    Dependency of standardised uptake values of fluorine-18 fluorodeoxyglucose on body sizecomparison of body surface area correction and lean body mass correction

    Nucl. Med. Commun.

    (1996)
  • L.M. Hamberg et al.

    The dose uptake ratio as an index of glucose metabolismuseful parameter or over-simplification

    J. Nucl. Med.

    (1994)
  • R.E. Coleman

    PET in lung cancer

    J. Nucl. Med.

    (1999)
  • L. Sokoloff et al.

    The (14C)-deoxyglucose method for measurement of local cerebral glucose utilisation: theory, procedure and normal values in the conscious and anaesthetised albino rat

    J. Neurochem.

    (1977)
  • M.E. Phelps et al.

    Tomographic measurement of local cerebral glucose metabolic rate in humans with [18F]-fluoro-2-deoxy-d-glucosevariation of method

    Ann. Neurol.

    (1979)
  • R.A. Hawkins et al.

    Effects of temporal sampling, glucose metabolic rates and disruption of the blood–brain barrier on the FDG model with and without a vascular compartment: studies in human brain tumours with PET

    J. Cereb. Blood Flow Metab.

    (1986)
  • C.S. Patlak et al.

    Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data

    J. Cereb. Blood Flow Metab.

    (1983)
  • K. Herholz et al.

    The influence of tissue heterogeneity on results of fitting non-linear model equations to regional tracer uptake curveswith an application to compartmental models used in positron emission tomography

    J. Cereb. Blood Flow Metab.

    (1987)
  • K. Schmidt et al.

    Fluorine-18-fluorodeoxyglucose PET to determine regional cerebral glucose utilisationa re-examination

    J. Nucl. Med.

    (1996)
  • A.A. Lammertsma et al.

    Measurement of glucose utilisation with [18F]-fluoro-2-deoxy-d-glucosea comparison of different analytical methods

    J. Cereb. Blood Flow Metab.

    (1987)
  • A.M. Spence et al.

    Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1-[C-11]glucose and FDGanalysis of the FDG lumped constant

    J. Nucl. Med.

    (1998)
  • H. Minn et al.

    [18F]-fluorodeoxyglucose uptake in tumourskinetic vs steady-state methods with reference to plasma insulin

    J. Comput. Assist. Tomogr.

    (1993)
  • A.C. Kole et al.

    Standardised uptake value and quantification of metabolism for breast cancer imaging with FDG and l-[11C]tyrosine PET

    J. Nucl. Med.

    (1997)
  • Cited by (1541)

    • How to Report PSMA PET

      2024, Seminars in Nuclear Medicine
    View all citing articles on Scopus
    View full text