The role of PET in monitoring therapy

Abstract

Positron emission tomography (PET) is being increasingly used for the evaluation of patients with known or suspected cancer at all phases of the management process from diagnosis, through staging to follow-up after treatment. The role of PET in therapeutic monitoring is expanding rapidly due to its ability to provide earlier and more robust identification of non-responders than provided by conventional non-invasive imaging approaches. PET can thereby potentially provide important benefits to the individual patient by allowing an earlier change to alternative treatments that may be more efficacious or by avoiding the unnecessary toxicity related to ineffective therapy. As therapies become ever more expensive, this could also produce cost savings because of earlier termination of ineffective treatment. Conversely, PET may demonstrate important biological effects despite a lack of apparent morphological response and therefore prevent premature withdrawal of effective therapies. Globally, the vast majority of therapeutic monitoring studies use the glucose analogue, fluorine-18 fluorodeoxyglucose (FDG) but new tracers such as fluorine-18 fluorothymidine (FLT) also offer promise for this application. In this review, the potential benefits and limitations of FDG PET are discussed along with suggestions regarding the most practical methodologies for response evaluation using this modality.

Figure 1

On baseline PET scanning of a patient with widely metastatic malignant melanoma obtained before planned chemotherapy (above) a representative coronal image plane demonstrates foci of intense uptake in the left external iliac nodal stations (arrows) and at other sites not displayed in this plane. The iliac nodes measured up to 15 mm. Following three cycles of chemotherapy there was no change in the CT appearances but PET suggested a complete metabolic response (below). While cure is unlikely in this clinical setting, a favourable metabolic response encouraged ongoing therapy and may have prognostic implications. Normalisation of the images on hepatic activity enables qualitative evaluation of response.

Figure 2

Despite a very favourable response in lung lesions between baseline (left upper) and follow-up (middle upper) CT scans, FDG PET (middle centre) demonstrated ongoing metabolic abnormality consistent with only a partial metabolic response. Fused PET/CT images (left and middle lower) potentially enable partial volume correction. Baseline (right upper) and post-treatment (right lower) maximum intensity projection (MIP) images also revealed minimal metabolic response despite a clinical reduction in the size of cervical lymph nodes.

Figure 3

Representative, co-registered FDG PET images (above) and fused PET/CT images (below) in the transaxial plane are demonstrated from a patient with a large, centrally necrotic GIST tumour at baseline (left) and 4 months after commencing imatinib (Glivec) (right). The hypermetabolic rim of the tumour had demonstrated a marked reduction in uptake within 1 week of commencing therapy (not shown) but the hypodense lesion on CT had increased slightly in size on follow-up. An ongoing metabolic response allowed the patient to remain on therapy with ongoing symptomatic benefit.

Figure 4

Maximum intensity projection (MIP) images (above) of the baseline (left) and follow-up (right) FDG PET studies demonstrate a change in the distribution of metabolic abnormality from focal uptake related to a known non-small cell lung cancer to a geographic pattern consistent with radiation pneumonitis within a radiation portal. The reference transaxial CT images at the level of the primary tumour in the right mid-zone (upper) demonstrate almost complete resolution of the primary lesion but progressive pleurally based changes. Corresponding transaxial PET (middle right) and PET/CT fused (lower right) images following treatment demonstrate no uptake in the primary tumour site but increased activity related to the radiographic abnormality. Based on the pattern of abnormality, no further treatment was given. Although progressive radiation fibrosis of the lung was observed, no local recurrence has been confirmed. The SUV in the presumed area of pneumonitis was similar to that recorded for the primary tumour at baseline demonstrating the limitations of relying purely on semi-quantitative measures to differentiate between benign and malignant processes.