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Diagnosis

Positron emission tomography (PET): experience with a large-field-of-view three-dimensional PET scanner

Positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) is an accurate technique for staging and therapeutic monitoring in oncology. We evaluated our use of FDG PET in an oncology centre after our first 2500 studies, and summarise our experience of PET for the major referral indications. Optimised for clinical service, PET offers lower scanning costs and therefore improved cost-effectiveness.

Rodney J Hicks, David S Binns, Meagan E Fawcett, Robert E Ware, Victor Kalff, Allan F McKenzie, John P Zalcberg and Lester J Peters

MJA 1999; 171: 529-532
For related articles see Morris

Introduction - Major referral indications - Providing cost-effective PET in oncology - Conclusion - Acknowledgements - References - Authors' details
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Introduction There is increasing recognition of the role of positron emission tomography (PET) in oncology, supplementing its established roles in the evaluation of myocardial viability1 and epilepsy.2 The radiopharmaceutical fluorine-18 fluorodeoxyglucose (FDG), an analogue of glucose, has high uptake in a wide range of tumours. FDG PET has been shown to be an accurate technique for tumour staging3 and for therapeutic monitoring.4

However, the high establishment and operating costs of conventional PET facilities make economic justification more difficult than for cheaper imaging methods. Before funding new technologies, government and third-party payers increasingly require evidence of cost-effectiveness as well as diagnostic accuracy. High unit scanning costs demand substantially greater effectiveness. The development of lower-cost positron imaging systems over the past 10 years offers a realistic opportunity to expand the clinical availability of PET by improving this balance.

Our PET facility, which uses such a system and is optimised for clinical service provision, was commissioned in September 1996. Our aim was to summarise our experience of PET scanning after the first 2500 FDG PET studies performed at our centre (Figure 1).


Major referral indications

Lung cancer

The most common referral indication was known or suspected lung cancer -- 522 studies (20%). Our preliminary, prospective evaluation of the impact of PET scans on the management of 47 consecutive lung cancer patients found that, in over 60% of cases, management was significantly influenced by the scan result (Figure 2).16 In particular, in 32% of patients being considered for treatment with curative intent, management was changed to palliative therapy after documentation of previously unrecognised extrathoracic disease.

In a more recent review limited to 140 consecutive patients being staged before definitive treatment of non-small-cell lung cancer, we found that PET changed treatment intent or modality in 47 patients (33%), altered delivery of the intended therapy in 39 patients (28%), and confirmed that the intended therapy was appropriate in only 39 patients (28%). In 15 patients (11%), an abnormality on PET, subsequently confirmed at follow-up, was ignored, with adverse outcome in all but two patients.

Melanoma

Assessing resectability of clinically localised metastatic disease in melanoma and staging of high-risk primary malignant melanoma have also been frequent indications -- 386 studies (14%) (possibly reflecting the presence of a dedicated melanoma unit at our institution).

Based on data suggesting excellent accuracy of FDG PET for staging malignant melanoma,8 we have recently performed a comparison of this technique with high-dose gallium-67 (Ga-67) scanning, previously the standard functional imaging technique for high risk melanoma at our institution. This prospective comparison in 108 patients demonstrated concordance between these investigations in over 80% of cases.17 However, in a limited number of patients, absence of gallium avidity in metastatic melanoma deposits led to striking discordance between FDG PET and Ga-67 results (Figure 3). As FDG PET is a much more convenient study for patients, being completed in less than three hours (whereas Ga-67 requires scanning up to a week after injection), we have largely replaced Ga-67 scanning with PET for this indication at our institution.

Head and neck cancer

After surgery or radiotherapy, normal tissue planes can be scarred and disrupted. This complicates structural imaging or clinical examination for evaluation of residual or recurrent head and neck cancer. Thus, restaging was the most frequent indication for PET among the 318 studies (13%) in this subgroup. A preliminary review of our experience with FDG PET in 72 patients with head and neck cancer showed a positive predictive accuracy of 92% and a negative predictive accuracy of 100% for restaging.18

Gastrointestinal malignancy

Referrals of patients with gastrointestinal malignancy (251 studies --10%) have mainly been after primary management. Confirmation of resectability of apparently localised metastatic disease or suitability for local radiotherapy have been the major clinical indications.

In a preliminary review of our experience in 41 patients,19 PET altered clinical management in 21 patients (52%), including 14 patients whose management was converted from aggressive locoregional therapy to palliative treatment based on demonstration of previously occult metastases (Figure 4).

Breast cancer

Evaluation of suspected recurrent or residual disease after treatment of breast cancer (190 studies -- 8%) has been the most common reason for referral of patients with breast cancer.

Epilepsy

Of the non-oncological indications, localisation of epileptogenic foci of complex partial seizures (88 studies -- 4%) was the most common reason for FDG PET studies.

A recent review of our experience in epilepsy involving 52 patients demonstrated a sensitivity for localisation of a seizure focus of 83% versus only 49% by volumetric magnetic resonance imaging (MRI) in the same patient cohort.20 Of 20 patients with localising PET studies who have undergone surgery, 18 are currently seizure free and the other two have had a single seizure associated with drug withdrawal (unpublished data).


Providing cost-effective PET in oncology

Cost-effectiveness

Despite an increasing body of evidence supporting the accuracy of FDG PET in oncology,5-7,9-15,21 its high cost and limited cost-effectiveness data have militated against funding for routine clinical use.

In the United States, FDG PET scanning has been shown to be a cost-effective alternative to conventional diagnostic methods of assessing solitary pulmonary nodules22 and staging non-small-cell lung cancer,23 and now attracts reimbursement for these indications. US government funding of PET scans has recently been extended (on the basis of as yet unpublished cost-effectiveness analyses) to evaluation of suspected recurrent colorectal cancer and staging of melanoma and lymphoma (in place of high-dose gallium-67 scanning).

In the United Kingdom, because of a reduction in surgical procedures, cost-effectiveness of PET for lung cancer staging has been reported.24 Our own preliminary data suggest a significant management impact of PET on lung cancer.16

Cost-benefit analyses to justify the use of FDG PET have shown significant savings even when based on costs derived from conventional PET facilities (quoted at US$1200, which includes technical and reporting costs).23

The ultimate cost of clinical PET scans depends on throughput of patients, availability and cost of radiopharmaceutical supplies, and the case mix of PET studies. Further evolution of lower-cost positron imaging devices and the development of production and distribution facilities to supply FDG to sites remote from a cyclotron have the potential to further reduce costs. If the cost of PET scans becomes more competitive, the merit of funding of PET for clinical use could be argued not on the basis of cost, but on its proven diagnostic and prognostic accuracy compared with standard investigations.

A clinical service model

As clinical service provision has been the major focus at our facility, our equipment and staffing reflect this orientation. Most other PET centres have focused on performing basic research as well as clinical studies. The capital and human establishment costs needed to perform the complex investigative studies that advance and validate PET technology increase the overall operational costs of such centres.

The PET scanner at Peter McCallum Cancer Institute (GE Quest-300H, UGM Medical Systems Inc, Philadelphia, Pennsylvania, USA) uses scintillation crystals similar to those used in standard nuclear medicine gamma cameras. This significantly reduces the purchase price compared with conventional PET scanners. However, the documented spatial resolution and sensitivity are similar to current generation three-dimensional PET scanners.25 The larger axial field-of-view (25 cm v 16 cm) allows higher patient throughput. For example, whole-body imaging studies can be completed in less than an hour.

The scanner characteristics limit administered radioacitivity to around 111 MBq (3 mCi) of F-18 FDG, compared with the typical dose of 300-555 MBq (8-15 mCi) with conventional PET scanners. This reduces operating costs, but limits the potential use of more short-lived PET tracers.

Unlike amortisation costs, which fall, radioisotope costs increase as the number of patients studied per day increases. Because of radioactive decay, patients studied late in the day require far more isotope to be dispensed at the time of production. Decay also occurs during transport, and therefore proximity of the end-user to the cyclotron also influences daily isotope requirements and costs. A more sensitive scanner has particular advantages when used at a site remote from the production cyclotron.

We believe that the relatively low start-up costs, high throughput and reduced operating expenses enable our facility to offer clinical PET studies at a cost that is significantly less than that generally quoted in the literature.

Even with the lower cost of our model of practice, PET is likely to remain more expensive than other tomographic diagnostic procedures commonly used in cancer staging and therapeutic monitoring. However, the relatively poor diagnostic accuracy of these tests, when used alone, means that multiple investigations are often used or tests are supplemented by invasive staging procedures, making overall costs considerably higher. The advantages to patient quality of life of more accurate staging, particularly that which spares futile surgical intervention or reduces patient anxiety by timely assessment of therapeutic response, although more difficult to express in economic terms, can not be underestimated.

Conclusion PET scanning has been available at our institution for three years. During this time it has been readily adopted by clinicians for planning of cancer management and for therapeutic monitoring. The high proportion of referrals from outside our institution suggests that there is growing awareness and high clinical acceptance of this technology among the medical community. Our own preliminary data support its utility in a wide range of oncological settings. More detailed prospective evaluation of the diagnostic accuracy and impact of PET in our institution is in progress and will help to further define the role of F-18 FDG PET in clinical oncology. By reducing scanning costs, the model of practice proposed offers the potential for PET to be become more widely available to the Australian community as a clinical rather than a research investigation.


Acknowledgements
Thanks to the staff of the cyclotron facilities at the Austin and Repatriation Medical Centre and the National Medical Cyclotron for providing timely supply of isotopes for clinical studies. We also thank the staff of our Department of Nuclear Medicine for taking on significantly increased work-loads with only a minimal increase in staffing levels, and Dr John Morris, the Chief Executive Officer of Peter McCallum Cancer Institute, for his ongoing support of the PET Program.

References
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(Received 1 Jul, accepted 5 Oct, 1999)

Authors' details The Peter MacCallum Cancer Institute, Melbourne, VIC.
Rodney J Hicks, MD, FRACP, Director of Diagnostic Imaging.
David S Binns, DipAppSci, ANMT, Chief Nuclear Medicine Technologist.
Meagan E Fawcett, BAppSci, ANMT, Nuclear Medicine Technologist.
Robert E Ware, MB BS, FCP(South Africa), Honorary Physician in Nuclear Medicine; currently, Director, Hobart Isotope Imaging, Hobart, TAS.
Victor Kalff, MB BS, FRACP, Honorary Physician in Nuclear Medicine; currently, Deputy Director, Alfred Hospital, Melbourne, VIC.
Allan F McKenzie, MB BS, FRACR, Director of Radiology.
John R Zalcberg, PhD, FRACP, Professor, and Director of Medical Oncology.
Lester J Peters, MD, FRACR, Professor, and Director of Radiation Oncology.

Reprints: Dr R J Hicks, Director of Diagnostic Imaging, Peter MacCallum Cancer Institute, Locked Bag 1, A'Beckett Street, Melbourne, VIC 3000.
rhicksATpetermac.unimelb.edu.au

©MJA 1999
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Figure 1
  • The primary referral diagnosis was that prospectively assigned at the time of the PET study.
  • Oncological indications were grouped by system (eg, "lung cancer" primarily comprised patients with non-small-cell tumours, but also included small-cell lung cancer and solitary pulmonary nodule).
  • All imaging performed on a given day was counted as a single study. Almost all oncology patients had screening of areas remote from the known or suspected site of the primary tumour.
  • The referral indication was known or suspected cancer in 2390/2500 cases (95.6%); 1881 individual patients had scans, with 619 follow-up studies in 379 patients for therapeutic monitoring or restaging after treatment.
  • More than a third of our referrals were from clinicians without formal affiliation with our institution, including referrals from all States and Territories.
  • The main referral indications at our facility reflect those cancers which have been shown to be accurately evaluated by PET - including lung cancer, 5-7 melanoma, 8,9 head and neck cancer, 10 colorectal cancer, 9 lymphoma, 9,11,12 and breast cancer. 13-15
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Figure 2 Figure 2. Non-small-cell lung cancer was diagnosed at bronchoscopy. A computed tomography scan was equivocal for mediastinal disease. FDG PET scanning of the thorax and abdomen was performed to assess suitability for surgical resection. The primary tumour (large arrows) and mediastinal nodal metastasis (small arrows) are clearly identified in transaxial (upper panel), sagittal (middle panel) and coronal (lower panel) projections. The patient was offered chemoradiotherapy rather than surgery.
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Figure 3 Figure 3: After resection of a melanoma of the left cheek, a palpable lymph node was shown (by fine-needle aspiration biopsy) to be a metastasis. A high-dose gallium-67 scan (left panel), which included tomographic imaging, did not demonstrate significant abnormality, so radical neck dissection was considered. Whole body FDG PET scanning (right panel) demonstrated disseminated metastases (arrows). The patient was spared unnecessary neck dissection and offered systemic therapy.
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Figure 4 Figure 4. After resection of a Duke C rectal carcinoma, this patient had rising carcinoembryonic antigen (CEA) levels and an apparently solitary hepatic metastasis (found at laparotomy - large arrow in left panel). At operation, a small bowel obstruction was thought to be related to postsurgical adhesions. FDG PET, performed to evaluate the patient's suitability for subsequent hepatic resection (right panel), demonstrated previously unrecognised widespread metastases (small arrows) and the patient was spared further futile surgery. Chemotherapy was commenced.
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