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Nuclear-medical review

Overview

Techniques from the field of nuclear medicine have been used for diagnostic and therapeutic purposes for over 50 years already, and for many years now, positron emission tomography (PET) has been an integral part of tumor diagnostics. PET is a functional/metabolic imaging technique, i.e. a method to visualize metabolic processes of body tissues by using a tracer substance (marker). This tracer consists of a glucose analogue which is marked with the radioisotope F-18 and is metabolized by the human body exactly like unmarked glucose. It is a radioactive drug that is subject to mandatory quality tests. Tumor diagnostics take advantage of the fact that malignant tumor cells metabolize more glucose due to their faster growth. The radiation of the tracer is measured by means of special crystals in a circular array. Due to the production of highly sensitive crystals and due to their dense geometrical alignment, the optical resolution of PET scans has increased and they have become more and more precise over the years. Besides, in modern PET/CT units the duration of an examination could meanwhile be reduced to about 15 minutes. For an exact analysis of a PET, a computed tomography (CT) is performed in addition in order to enable a correction for attenuation of the PET and to enable that the recorded tracer accumulation can be related to the anatomical structures and potential pathological changes. The PET/CT examination can either be performed as a low-dose CT with reduced spatial resolution and/or as a diagnostic CT with high spatial resolution. Which of these is indicated depends on the individual case. This procedure requires a maximum degree of specialist knowledge and experience in this field.

PET is a diagnostic procedure with therapeutic consequences and is becoming increasingly important in Hodgkin lymphoma, where it is used in particular to differentiate between vital tumor tissue and scarred residual tissue. Treatment decisions regarding whether radiotherapy is required or not are based on PET results, both during chemotherapy and after completion of chemotherapy.

PET in Hodgkin lymphoma patients

Since the beginning of the 5th trial generation of the GHSG (HD15 for advanced stages of Hodgkin lymphoma), PET has been used as an examination technique. In this trial, patients with a residual tumor ≥ 2.5 cm received an FDG-PET. The complete cross-sectional diagnostic images were reviewed by an interdisciplinary expert panel. The high negative predictive value of the PET examination has also been described in the literature and on this basis, patients with a negative PET result (no tracer accumulation in the residual tumor tissue) were not irradiated. Radiotherapy was only performed on those patients with PET-positive residual tumor tissue after chemotherapy. With this approach the negative predictive value of FDG-PET could be tested in a large number of patients and, moreover, for PET-negative patients the toxicity of therapy could be reduced. The GHSG’s HD15 trial for advanced stages of Hodgkin lymphoma proved PET to possess a very high negative predictive value after chemotherapy (94%).

The 6th trial generation (HD18 for advanced stages of Hodgkin lymphoma) has started in May 2008. In this trial a PET examination is already performed after 2 cycles of chemotherapy, after which patients are randomized. In case of a negative PET result, the trial aims to prove the non-inferiority of a treatment reduction to 4 cycles of escalated BEACOPP, and in case of a positive PET result, it aims to test the improvement of progression-free survival by adding rituximab to therapy. After completion of chemotherapy, patients with residual tumor tissue ≥ 2.5 cm receive another PET and if the result is positive, residual tumor tissue ≥ 2.5 cm is irradiated.

In the HD16 trial for early stages of Hodgkin lymphoma, a PET is performed after end of chemotherapy, which consists of 2 cycles. In case of a positive PET result, patients are irradiated afterwards, and in case of a negative PET result, patients are randomized to be irradiated or not. This trial aims to test whether radiotherapy can be omitted in patients with metabolic remission after chemotherapy (PET-negative patients).

Assessment criteria

For PET assessment the criteria described in Juweid and Cheson in the Journal of Clinical Oncology 2007 are applied.

For PET assessment in HD16-18 the following additional key was introduced to describe the intensity of the glucose metabolism:

  • 0 = PET negative, no FDG uptake in residual tumor tissue
  • 1 = PET negative, mild FDG uptake, not more intensive than mediastinal blood pool
  • 2 = PET positive, moderate FDG uptake, more intensive than mediastinal blood pool
  • 3 = PET positive, intense FDG uptake
  • 4 = not assessable, e.g. if physiological accumulations are closely adjoining a potential pathological accumulation; to be treated like PET positive
  • 5 = not examined; the site was not included in the examination

This key for describing the glucose metabolism is used internationally and was developed and agreed upon on two international conferences by study groups and experts (on the International Workshop on Interim PET in Lymphoma in Deauville/France in 2009 and in Menton/France in 2010).

Tasks of the nuclear-medical review center

  • To consult nuclear-medical examiners and oncologists by reassessing PET/CT examinations
  • To organize the expert panel meetings required within the scope of the HD18 trial for early assessment of treatment response by means of PET/CT
  • To organize the expert panel meetings of the HD16 and HD17 trial

Members of the nuclear-medical review center

  • Professor Dr. med. M. Dietlein
    Department of Nuclear Medicine of the University of Cologne, specialist for diagnostic radiology and nuclear medicine
  • PD Dr. med. C. Kobe
    Department of Nuclear Medicine of the University of Cologne, specialist for nuclear medicine
  • G. Kuhnert, assistant physician
    Department of Nuclear Medicine of the University of Cologne
  • Dr. med. A. Holstein
    Department of Nuclear Medicine of the University of Cologne, specialist for diagnostic radiology
  • D. Kahraman, assistant physician
    Department of Nuclear Medicine of the University of Cologne

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