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Letters |
Medical College of Georgia
Augusta, GA 30912
In their article in the April 2005 issue of the AJR, Drs. Uematsu et al. [1] concluded, "the detection of osteoblastic [metastatic bone] lesions is limited on FDG PET." Based on their methodology, this conclusion is difficult to accept and contradicts those of other reports in the literature.
The study conducted by Uematsu et al. [1] was based on a lesion-by-lesion analysis of 15 patients, with 149 lesions occurring in four patients, three of whom were assessed for restaging presumably after chemotherapy when the metabolic uptake of 18F-FDG may have been moderated by this therapy. Fourteen lesions were seen in three other patients, two of whom were assessed for restaging presumably after chemotherapy. Eight patients had no metastatic bone lesions listed. Their conclusion is, therefore, based on seven patients, five of whom were assessed for restaging presumably after chemotherapy, with 163 metastatic bone lesions (Table 1 [1]).
In the Results section, Uematsu et al. [1] base their statistical analysis on 900 lesions. It is unclear where the 737 lesions not listed in Table 1 came from. There were no false-positive lesions seen on FDG PET, which is remarkable because the specificity of FDG PET is limited by metabolically active benign lesions (acute fractures, active osteomyelitis, Paget's disease, fibrous dysplasia) [2]. The 18F-FDG dose (220-240 MBq [6-6.5 mCi]) was significantly lower than the standard adult dose of 370-555 MBq (10-15 mCi), which, as the authors pointed out, may have compromised lesion detectability. It was not stated how lesions were classified as positive or negative for metastasis by PET. There was no tissue confirmation of metastatic bone lesions. There was no semiquantitative analysis (standardized uptake value) listed. Enhanced color PET images were shown as examples, and depending on color-scale adjustment, visual analysis of color images may be misleading. Coregistration of PET and CT images (PET/CT) is proving more accurate than PET alone (as used for this article [1]) or CT alone.
In the Subjects and Methods section, the authors state, "Eight patients were evaluated for restaging and seven for initial staging." In Table 1, they state seven patients were evaluated for restaging and eight for initial staging.
Other studies report FDG PET is superior to bone scanning in the detection of bone metastases [3]. The evidence-based guidelines established by the American Society of Clinical Oncology state the following [4]:
A bone scan is optional in patients who have evidence of bone metastases on FDG PET scanning, unless there are suspicious symptoms in regions not imaged by FDG PET.... A nonrandomized, prospective study comparing FDG PET with bone scan in 53 patients with lung cancer found that PET was superior to bone scan in detecting bone metastases, producing no false-negatives, which is in contrast to six false-negatives produced by bone scan.... A nonrandomized, retrospective study of 110 consecutive patients who underwent both FDG PET and bone scan found FDG PET to have superior accuracy in detecting bone metastases (96% versus 66%) suggesting that whole-body FDG PET may be a useful substitute for bone scanning in detecting bone metastases.
Based on small study size and other potential limitations discussed, it does not seem valid to state that FDG PET is limited in the detection of metastatic bone lesions based on the results from this article alone.
References
Shizuoka Cancer Center Hospital
Nagaizumi, Shizuoka 411-8777,
Japan
The intention of our report [1] was to pay attention to the usefulness of bone scanning, especially bone SPECT, to detect bone metastases in patients with breast cancer, not in those with other cancers, such as lung cancer. The goal was to see whether the use of FDG PET can replace bone scanning to diagnose bone metastases from less aggressive tumors, such as breast cancer.
The time course to the appearance of clinically detected distant metastases of breast cancer is extremely long. It is common for metastases to manifest 10 years or more after the initial diagnosis of breast cancer [2]. In the long duration of manifestation of bone metastases, many breast cancer patients, except the low-risk subset who never develop bone metastases, are treated with adjuvant hormone therapy or chemotherapy (or both) according to guidelines [3]. Adjuvant hormone therapy, chemotherapy, or both may change purely osteolytic lesions into mixed or osteoblastic bone metastases [4].
Breast cancer is a heterogeneous disease, and some patients, whose survival duration may be a few months, have aggressive disease. FDG PET may be helpful in a carefully selected subgroup of patients with an advanced stage of breast cancer because the advantage of whole-body FDG PET is its ability to detect metastases in different sites and organs in a single examination. Patients with advanced stages of breast cancer who have no treatment options may have osteolytic lesions with high FDG uptake levels. However, these osteolytic lesions may be detected by conventional diagnostic imaging, and these patients with advanced breast cancer may have osteosclerotic lesions also. Therefore, osteoblastic metastases with advanced breast cancer may be undetectable by FDG PET.
Bone scanning is not recommended for patients with stage I or II breast cancer because of low return. Some studies have shown that most patients are symptomatic at diagnosis of bone metastases [5]. Many breast cancer patients have more indolent disease that is responsive to hormone therapy or chemotherapy. With adjuvant hormone therapy, chemotherapy, or both, breast cancer tends to result in mixed bone metastases [4]. On bone scanning, the false-negative rate was only 0.08% in 1,267 consecutive cases of breast cancer [6]. These results suggest that cases of breast cancer, especially stages I and II postoperative breast cancer, with purely osteolytic metastases only are not common.
Our results that bone scanning is more sensitive than FDG PET for osteosclerotic lesions and that FDG PET detects more abnormalities than bone scanning for osteolytic lesions agree with previously documented findings [7]. Therefore, my coauthors and I disagree with Drs. Williams and Smith who stated that our conclusion is difficult to accept and contradicts those of other reports in the literature. Some reports indicate that FDG PET has a lower sensitivity for detecting breast cancer bone metastases than bone scanning [8, 9]. Moreover, some reports indicate that a relatively low sensitivity in the detection of bone metastases can also be seen with FDG PET [10, 11].
There is currently no established role for FDG PET in the clinical evaluation of bone metastases from breast cancer. Bone SPECT has improved both the sensitivity and the specificity of bone scanning because the precise location of lesions can be seen on tomographic images [12-16]. Our study is the first to compare bone SPECT and FDG PET [1].
Williams and Smith have misunderstood the Subjects and Methods section of our article [1]. Our patient 3, who had synchronous lung metastases, was evaluated for initial staging. Therefore, eight patients were evaluated for restaging and seven were evaluated for initial staging. That is to say, eight patients had been treated with adjuvant hormone therapy, chemotherapy, or both before undergoing bone scanning and FDG PET and seven patients had undergone no treatments. We had no false-positive lesions seen by FDG PET after confirmation by MDCT and MRI.
We stated in our article [1] that the injected doses in the range of 220-240 MBq might reduce the sensitivity of FDG PET and lower injected doses of FDG were typically given in Japan because most Japanese patients are smaller than Western patients. Moreover, we stated in our article [1] that we had no tissue confirmation of metastatic bone lesions; confirmation was by MDCT and MRI or clinical follow-up of more than 12 months. Even fine-needle aspiration cytology and core needle biopsy can be affected by sampling errors. Quantitative methods may be used to complement visual image analysis for benign and malignant lesions. However, this practice is not universal. We used visual assessment in the interpretations of the FDG PET images.
In summary, understanding the advantages and the disadvantages of bone scanning and FDG PET in detecting bone metastases in breast cancer patients will assist clinicians in screening patients and planning treatment. FDG PET and bone scanning might be complementary in their ability to detect bone metastases in breast cancer. Routinely performed bone SPECT is practicable and cost-effective and improves the sensitivity and specificity of bone scanning. FDG PET is not a powerful tool for the detection of breast bone metastases. Bone scanning still remains the most important investigation for the detection of bone metastases in patients with breast cancer. However, a larger study population and more outcome data are necessary to confirm our results.
References
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