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CLINICAL INVESTIGATIONS |
Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging Clinic/Nuclear Medicine, University of California, Los Angeles, School of Medicine, Los Angeles; and Northern California PET Imaging Center, Sacramento, California
| ABSTRACT |
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Key Words: PET colorectal cancer survey
| INTRODUCTION |
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Biologic tumor imaging with PET can overcome these limitations. PET using the glucose analog 18F-FDG is applied clinically to detect and stage a variety of cancers (46). The use of glucose metabolism to differentiate malignant tumors is based on the biology of neoplastic degeneration, which has been shown to exhibit high rates of glucose consumption in malignant tissue (4,7). This occurs because of a progressive loss of the tricarboxylic cycle to produce adenosine triphosphate (ATP). The production of ATP by glycolysis is amplified dramatically in tumor tissue. Neoplasms further increase their dependence on glucose by activation of the hexose monophosphate shunt to provide a carbon backbone to meet the high DNA and RNA synthesis requirements of cell proliferation (8).
Like glucose, FDG is a substrate for facilitated transport and is phosphorylated by hexokinase in tumor cells. However, FDG-6-PO4 is not catabolized and remains trapped in tumor cells. Therefore, the relative distribution of FDG-6-PO4 can serve as a marker of glucose metabolism in the organ systems of the body, which can then be imaged, with PET.
A high diagnostic accuracy of PET has been shown for staging many kinds of cancers (46,9) and specifically for staging and restaging (10) of colorectal cancer and for identifying the sites of metastatic involvement. Furthermore, the cost-effectiveness of PET imaging for managing patients with lung cancer, solitary pulmonary nodules, and colorectal cancer has been established (9,11,12).
To our knowledge, it has not been established previously how and whether referring physicians change their therapeutic approaches on the basis of information provided by PET. Thus, the true impact of whole-body PET on managing patients with colorectal cancer, in the referring physicians perspective, is unknown. Therefore, the aim of this study was to determine, from the referring physicians point of view, the impact of whole-body PET imaging on the management of patients with colorectal cancer.
| MATERIALS AND METHODS |
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Image Acquisition and Reconstruction
An EXACT HR or HR+ system (CTI/Siemens, Knoxville, TN) was used to obtain whole-body PET images. The resolution of reconstructed images used in these studies was 812 mm for these devices. The characteristics of these scanners have been described (13,14).
No attenuation correction was performed at UCLA, where images were reconstructed using standard filtered backprojection. At the NCPIC, attenuation-corrected images were obtained and iterative image reconstruction algorithms were used (15,16).
After a 6-h fasting period, 555 MBq (15 mCi) FDG were injected. Whole-body imaging was started 45 min later. Images were acquired from six to nine bed positions (6 min per bed position) in each patient. The acquired image sets were displayed on transaxial images and coronal and sagittal views.
The three-dimensional volume was inspected on the monitor.
Image Interpretation
The PET studies were not read blinded but were always interpreted within the context of a clinical readout session (i.e., knowledge of patient history as well as reports of other imaging tests). Thus, PET reports were based on all available clinical information in addition to the PET images. No quantitative or semiquantitative analysis of FDG uptake in lesions, such as by standardized uptake value, was performed because this is not part of the clinical routine image interpretation at our institutions.
To evaluate the impact of PET imaging on patient management, pre-PET and post-PET questionnaires were sent to the referring physicians (Fig. 1). This was done as a single faxed protocol. This simple straightforward approach was chosen to increase the likelihood of receiving a response from referring physicians. A letter explaining the purpose of the study was attached to the survey. However, to avoid bias, the participating physicians did not receive any additional reminder or any other information related to the study. The pre-PET questionnaire asked to specify the patient stage and management plan before PET, whereas the post-PET questionnaire inquired about PET-induced changes. Two parameters were analyzed: changes in patient stage and changes in patient management. Management changes were classified into two categories: Intermodality changes were defined as changes between treatment modalities (from surgery to radiation therapy), and intramodality changes were defined as changes within one treatment modality (e.g., from one chemotherapeutic agent to another).
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| RESULTS |
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Specialties of all referring physicians (responders and nonresponders) included medical oncologists (54%), surgeons (23%), general practitioners (19%), radiation oncologists (3%), and pulmonologists (1%). The distribution of specialties of the 60 responding physicians included 53% medical oncologists, 27% surgeons, 15% general practitioners, 2% radiation oncologists, and 3% other specialties. Similarly, the distribution of specialties of the 86 nonresponding physicians included 53.5% medical oncologists, 21% surgeons, 21% general practitioners, 3.5% radiation oncologists, and 1% pulmonary specialists. The distribution of specialties did not differ significantly between UCLA and the NCPIC.
Clinical Indications for PET Study
FDG PET was ordered for more accurate staging in 55% of the cases, for monitoring the course of the disease in 23%, for more accurate diagnosis in 12%, for monitoring therapy in 2%, and for a combination of these reasons in 5% of the cases. The remaining 3% reported other reasons for ordering the scan. The clinical indications for the PET study did not differ between the study centers.
Pre-PET Clinical Management Plan
The intended treatment before PET was surgery in 36.5%, medical treatment in 27%, radiation in 3%, and a combination of treatments in 5%. No further treatment was planned in 27%, whereas the remaining 1.5% of the respondents stated other treatments.
Impact of PET on Clinical Stage
Changes in clinical stage were reported for 25 patients (42%): 20 (33%) were upstaged and 5 (8%) were downstaged. Thirty-two patients (53%) had no change in clinical stage. No response to this question was received for the remaining 5% (Table 1).
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Table 2 specifies the management changes for each individual patient.
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| DISCUSSION |
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This survey-based study has several limitations. Fifty-nine percent of the surveys were not returned by the referring physicians, which likely introduced a "responder" bias. As a worst-case scenario, only supporters of PET might have responded, whereas those who believed that PET imaging was not useful for patient management might have refrained from participating in this study. However, assuming this scenario, PET would have affected the clinical stage and management in 17% and 21% of all patients, respectively. However, the response rate in one of the two study sites (NCPIC) was significantly higher (44%), decreasing the probability that the data were skewed in this direction. More important, the impact of PET on patient stage and clinical management did not differ between the two sites.
The response rate of 41% is likely explained by several factors. Varying interests in the subject of the survey, the length of the questionnaires, and other parameters affect response rates. In addition, less isolated and more "with-it" doctors tend to respond more frequently. A comparison between respondents and nonrespondents to our survey revealed no large bias. Cartwright (22) reported that the level of training and professional specialty did not vary between respondents and nonrespondents. In our survey, 53% of the respondents and 53.5% of the nonrespondents were oncologists, 2% and 3.5% were radiation oncologists, 27% and 21% were surgeons, and 15% and 21% were general practitioners. These differences in specialties between respondents and nonrespondents were not significant. Thus, a bias based on specialty can be ruled out. Furthermore, no significant differences were found between normal and abnormal PET scans for responders and nonresponders (normal and abnormal PET scans were found in 23% and 77% of the responders and in 30% and 70% of nonresponders). A recent study, which had a response rate of 43%, estimated the error introduced by such bias to range from 3% to 10% (23). These authors used a parallel survey to validate their findings and concluded that even response rates of 60%70% would not have altered their findings.
The accuracy of whole-body PET imaging for the staging of recurrent colorectal cancer has been established. Strauss et al. (24) examined 29 patients with colorectal cancer and found recurrent disease in 21. In the remaining 8 patients, masses that were suggestive of cancer on CT were ruled out by biopsy (n = 7) or surgery (n = 1).
A similar accuracy was reported by Delbeke et al. (10), who used FDG PET on 51 patients with suspected recurrent colorectal cancer. They showed that PET was more accurate than CT for characterizing both intrahepatic and extrahepatic lesions. In most of these patients, histopathology served as the gold standard.
Similar findings were reported by Schiepers et al. (3). They evaluated the clinical value of FDG PET in 76 patients who presented with or were suspected of having recurrent local or distant colorectal cancer. PET results were compared with those of routine imaging (CT of the pelvis, CT or sonography of the liver, and chest radiography). The accuracy of PET for local disease was 95%, which was superior to CT of the pelvis (accuracy, 65%). PET accuracy for liver metastases (98%) compared favorably with anatomic imaging (93%). Unexpected extrahepatic metastases were detected by PET in 10 patients. These authors concluded that the main value of PET was an improved staging of apparently resectable, local, or distant recurrent disease. Thereby, a more adequate indication of major secondary surgery could be attained (3). In that study, 20% of the patients were upstaged and about 5% were correctly downstaged by PET. These findings were confirmed subsequently in an expanded group of patients from the same institution (25). Valk et al. (21) addressed the diagnostic accuracy and cost-effectiveness of this PET imaging in 155 consecutive patients with recurrent colorectal cancer. In this prospective, blinded study the authors reported similar specificities for PET and CT (98% vs. 96%), yet a significantly higher sensitivity was reported for PET (93% vs. 69%). Specifically, PET proved to be more accurate than CT for detecting liver lesions, pelvic involvement, extrahepatic abdominal metastases, and retroperitoneal disease.
All of these studies provide the justification for including PET in the diagnostic work-up of patients with colorectal cancer. However, none of the studies has evaluated prospectively the impact of PET on the management of patients with colorectal cancer from a referring physicians point of view.
| CONCLUSION |
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| ACKNOWLEDGMENTS |
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| FOOTNOTES |
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For correspondence or reprints contact: Johannes Czernin, MD, Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging Clinic/Nuclear Medicine, University of California, Los Angeles, School of Medicine, AR-259 Center for the Health Sciences, Los Angeles, CA 90095-6948.
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