Molecular Imaging Insight - May 2008 - (Page 10) Evidence-based medicine In a prospective randomized trial from Holland, performed in patients otherwise being considered for surgical treatment, FDG-PET reduced futile thoracotomies by 25 percent. In a prospective series of patients being considered for curative chemoradiotherapy, my group in Australia demonstrated that FDG-PET altered management in more than 50 percent of cases. Importantly, approximately 25 percent of patients were found to have distant metastases that had not been recognized on conventional staging. Obviously, money spent on expensive and potentially morbid attempts at cure in such patients is illogical since these patients are doomed to fail and will still require the palliative or systemic therapies that they ought to have received up-front. Furthermore, another 25 percent of radiotherapy patients had their radiation treatment fields altered, primarily to include FDG-avid nodal metastases that were not enlarged on CT and therefore would not otherwise have been included in the treatment volume. Again, clearly it is a complete waste of a valuable resource such as radiotherapy to miss macroscopic disease sites. Although not all patients are cured with radiotherapy, even when all their disease is included in the radiation volume, it is a forlorn hope that patients with inadequate disease coverage will be cured. Those patients who miss the opportunity for cure will go on to require palliative treatment and contribute to the loss of productivity and the other societal costs associated with cancer mortality. It is said that cancer doesn’t touch an individual, it attacks a whole family. To go on using clearly inferior techniques for staging lung cancer is being penny wise but dollar foolish. Beyond the implications for an individual patient, there are important considerations for resource allocation rendered by more appropriate selection of patients for curative treatment. In many parts of the world, access to radiation oncology services is severely constrained and waiting times are long. During this delay, there is the potential for disease progression, making prior planning studies irrelevant to the current extent of locoregional disease or converting some patients from curative to only palliative candidates. By identifying a greater number of patients who are, by virtue of the extent of disease diagnosed only on PET, suitable only for palliative treatment, the course of radiotherapy is reduced from approximately six weeks to one week. This resource opportunity allows those in the queue to get their radiotherapy earlier. By better targeting locoregional disease, early local recurrences ought to also be reduced, minimizing the call on salvage radiotherapy and opening additional time on valuable linear accelerators. Similar arguments can be made about futile surgical procedures. Perhaps the greatest opportunity for PET to influence healthcare costs is in the arena of chemotherapy. Based on current response assessment criteria, which are related to changes in the dimensions of index lesions as measured on morphological imaging studies, there needs to be a significant increase in tumor 10 Molecular Imaging Insight | May 2008 burden before a chemotherapeutic regime can be considered to have failed due to progressive disease. However, particularly in cancer that has a relatively indolent natural history or that presents with relatively large tumor deposits, progression may be slow or reflect a huge increase in tumor volume before ineffective treatment is ceased. During this time, the cost and toxicity of this treatment is accumulating. The opportunities for a favorable response to subsequent therapies are compromised by the increased number of cancer cells that must now be obliterated and the compromised physical, physiological, emotional, and, often, fiscal reserves of the patient. Earlier response assessment has been a key feature of the majority comparative studies using PET and conventional response assessment and most also have demonstrated superior stratification of survival. Molecular therapeutics A final note must be made regarding the potential for PET to speed and simultaneously reduce the cost of cancer drug development. This is a huge topic, and well beyond the scope of this discussion. However, it is being increasingly recognized that metabolic imaging using PET can provide unique insights into drug effects. More robust proof-of-mechanism studies, selection of target populations, and assessment of response rates in better stratified groups will allow ineffective drugs to be culled at an earlier stage and effective drugs to be fasttracked to market. Hopefully, this will reduce the cost of these novel therapies and allow them to also be more rationally prescribed. The current cost of development of each new cancer drug has been estimated to be up to $1 billion and to take up to 14 years. With a current patent life of only 15 years, it is clearly difficult to provide shareholder returns on such an investment unless there is a very large market and a high cost for the drug. At the same time, there is a move away from so-called “block-buster” drugs toward personalized medicine with targeted therapies that will have niche applications. Unless new strategies for drug development are found, this new era of medical care will fail. I share the view that molecular imaging has a key role to play in drug development. Each individual brings his or her own emotional, physical, intellectual, experiential, supporting and fiscal resources to bear when diagnosed with cancer. Patients need to be informed not only of the cost of FDG-PET, but the implications of not having the most accurate disease evaluation available for many cancer situations. If we can discover the definitive blood test and a universally effective cancer therapy, we won’t need any imaging at all. Until that day, we can’t afford not to use PET. Professor Rodney J. Hicks, MD, is professor, Department of Medicine, the University of Melbourne, and director of The Centre for Molecular Imaging and Translational Medicine, The Peter MacCallum Cancer Centre in Melbourne, Australia. He also is an editorial advisory board member of Molecular Imaging Insight. MolecularImaging.net http://MolecularImaging.net
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