|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Originally published as JCO Early Release 10.1200/JCO.2007.11.2854 on June 25 2007 © 2007 American Society of Clinical Oncology. Fusion of Metabolic Function and Morphology: Sequential [18F]Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography Studies Yield New Insights Into the Natural History of Bone Metastases in Breast Cancer
From the Institute of Nuclear Medicine, University College London Hospitals National Health Service Foundation Trust, and University College London, London; and the Cancer and Imaging School, University of Manchester and Christie Hospital National Health Service Foundation Trust, Manchester, United Kingdom Address reprint requests to Yong Du, MD, PhD, Institute of Nuclear Medicine, 5th Floor, University College Hospital, 235 Euston Rd, London NW1 2BU, United Kingdom; e-mail: yong.du{at}uclh.nhs.uk
Purpose: By monitoring bone metastases with sequential [18F]fluorodeoxyglucose positron-emission tomography/computed tomography ([18F]FDG-PET/CT) imaging, this study investigates the clinical relevance of [18F]FDG uptake features of bone metastases with various radiographic appearances. Patients and Methods: Bone metastases were found in 67 of 408 consecutive patients with known/suspected recurrent breast cancer on [18F]FDG-PET/CT, characterized by CT morphology changes and/or bony [18F]FDG uptake. Twenty-five of the patients had sequential [18F]FDG-PET/CT examinations (86 studies) over an average follow-up period of 23 months. The temporal changes in [18F]FDG uptake and corresponding CT morphology features of 146 bone lesions identified in these 25 patients were followed up and correlated with therapeutic outcome retrospectively. Results: The 146 lesions were classified as osteolytic (77), osteoblastic (41), mixed-pattern (11), or no change/negative (17) on CT. The majority of the osteolytic (72; 93.5%) and mixed-pattern lesions (nine; 81.8%), but fewer of the osteoblastic lesions (25; 61%), showed increased [18F]FDG uptake. After treatment, 58 osteolytic lesions (80.5%) became [18F]FDG negative and osteoblastic on CT and only 14 relatively large lesions (19.5%) remained [18F]FDG avid. Of the 25 [18F]FDG-avid osteoblastic lesions, 13 (52%) became [18F]FDG negative, but 12 (48%) remained [18F]FDG avid and increased in size on CT. Five of the mixed-pattern lesions remained [18F]FDG avid after treatment. All 17 CT-negative lesions became [18F]FDG negative; however, nine of them became osteoblastic. None of the initially [18F]FDG-negative lesions showed [18F]FDG avidity during follow-up. Conclusion: [18F]FDG uptake reflects the immediate tumor activity of bone metastases, whereas the radiographic morphology changes vary greatly with time among patients.
The contribution of [18F]fluorodeoxyglucose positron-emission tomography ([18F]FDG-PET) imaging to the management of a variety of malignancies is now well recognized.1-3 However, its role in the evaluation of bone metastases has not been established adequately.2,4-6 Bone metastases are a frequent complication of cancer, occurring in up to 70% of patients with advanced breast cancer, for example. On the basis of radiographic appearance, they are classified as osteolytic, osteoblastic, or mixed-pattern if both elements are presented in the same lesion.7 The consequences of bone metastasis are often devastating, and novel treatments have been under intensive investigation.7-13 Techniques are required to identify patients with active bone metastases and to monitor treatment response in a timely manner.10,14 Bone scan using technetium-99m–labeled diphosphonates has been the method of choice for the detection of bone metastases, albeit with poor specificity.15 A positive bone scan reflects the existence of osteoblastic response, which may be secondary to either malignant or benign etiology. The osteoblastic response identified on bone scan persists for some considerable time and the scan therefore remains positive even if there is good response to treatment. Bone scan is thus unsuitable to evaluate treatment response.15 Other imaging modalities, such as computed tomography (CT) and magnetic resonance imaging, have also been found useful in the detection of bone metastases, but there has been no satisfactory technique for monitoring therapy response.8,15,16 The most recent Response Evaluation Criteria in Solid Tumors guidelines still consider bone metastases to be "nonmeasurable."17 [18F]FDG has been established as a PET imaging tracer for the detection and monitoring of numerous malignancies, owing to the increased glycolysis of most tumor cells.1,2 However, the results obtained when investigating [18F]FDG-PET in the detection of bone metastases have been conflicting, with sensitivity varying widely from 56.5% to 100%.5,15 Cook et al18 compared the [18F]FDG-PET findings with x-ray CT and observed a correlation between the [18F]FDG uptake features and the CT morphologies of bone metastases from breast cancer. [18F]FDG-PET was found to be superior to bone scan in the detection of osteolytic metastases, but significantly less sensitive in the detection of osteoblastic lesions (P < .05).18 This observation has been confirmed in subsequent studies.19-22 However, most of the patients included in these studies had been treated with systemic therapy,18-22 and it has been suggested that osteolytic bone metastases may become osteoblastic after effective treatment.23 Therefore, an important unanswered question that needs to be addressed is the clinical relevance of [18F]FDG-negative osteoblastic lesions, which are often positive on bone scan.4,5 The recently available hybrid PET/CT enables us to correlate directly the [18F]FDG uptake features with the CT morphology, and this would ideally be investigated by sequential [18F]FDG-PET/CT studies performed on the same patients treated during a certain time period. In this study, by following up retrospectively the same bone metastases with sequential [18F]FDG-PET/CT studies, we correlated the treatment status with the temporal changes in [18F]FDG uptake and the corresponding CT morphology of each bone lesion, thereby investigating the clinical relevance of [18F]FDG uptake features of bone metastases with various radiographic appearances.
Patients and Study Design During a 4.5-year period, 408 consecutive female patients with known or suspected recurrent breast cancer were referred to our institution for [18F]FDG-PET/CT study to assess the extent of the disease. Bone metastases were identified in 67 of these patients, with either highly suspicious or definite CT morphology changes or localized bony [18F]FDG uptake. Among them, 25 patients who had sequential [18F]FDG-PET/CT studies are included in this study, with 86 scans (scanning intervals, 2 to 9 months) performed over an average follow-up period of 23 months (range, 9 to 48 months) since the baseline [18F]FDG-PET/CT study. All of these patients had excision/biopsy-confirmed recurrent breast cancer and their demographic and clinical characteristics are summarized in Table 1. Eighteen of them had previous systemic therapies and 14 patients had radiotherapy. No patients had received anticancer therapy closer than 4 weeks before the baseline [18F]FDG-PET/CT study. On the baseline [18F]FDG-PET/CT images, 146 bone metastases were diagnosed in these 25 patients, and the temporal changes in [18F]FDG uptake and corresponding CT morphology features of these lesions were investigated semiquantitatively as measured by lean body mass–corrected maximum standardized uptake value (SUVmax)24 and followed up on subsequent [18F]FDG-PET/CT images. After baseline [18F]FDG-PET/CT studies, seven patients were administered hormonal therapy alone, and 18 patients received chemotherapy, either alone or in combination with other therapies. Seventeen patients also received radiotherapy. The [18F]FDG uptake changes of each bone lesion were correlated retrospectively to the CT appearances and the response to treatment.
Twenty-one of these patients also had serial bone scans during the [18F]FDG-PET/CT follow-up period, whereas four patients had bone scan only before their first [18F]FDG-PET/CT study. No patient had marrow-stimulating cytokine therapy. All patients consented for their data to be used for research.
[18F]FDG-PET/CT Imaging
Image Interpretation An [18F]FDG-negative lesion is defined as no increased [18F]FDG uptake as compared with adjacent bone tissue. The size of CT-negative lesions was estimated on fused images by measuring the boundary of increased [18F]FDG uptake. The boundary was selected by increasing the lower threshold of the image to the level where uptake in adjacent normal bone was no longer visible. The t test was used to assess the differences in [18F]FDG uptake intensity (SUVmax) in different groups of bone lesions. Kaplan-Meier survival curves25 were plotted comparing survival between groups with and without persistent [18F]FDG-avid bone metastases using the log-rank test.26
Distribution of Bone Metastases and [18F]FDG Uptake Intensity of Different Morphologic Types of Bone Metastases The distribution of the 146 identified bone metastases in the 25 patients, including [18F]FDG uptake features and the changes in radiographic morphology after therapy, is summarized in Table 2. Before additional treatment, the majority of the osteolytic (72; 93.5%) and mixed-pattern (nine; 81.8%) lesions, as well as a lesser percentage of the osteoblastic lesions (25; 61%), showed increased [18F]FDG uptake. However, the intensity of [18F]FDG uptake varied widely, as shown in Figure 1, in which the [18F]FDG uptake intensity (SUVmax) and the size of all 123 [18F]FDG-avid lesions are presented. For the 72 [18F]FDG-avid osteolytic lesions, the mean SUVmax (± standard deviation) was 5.25 ± 3.01 (range, 2.11 to 14.32). For the 25 [18F]FDG-avid osteoblastic lesions, the mean SUVmax was 4.62 ± 2.35 (range, 1.94 to 8.15). The difference between osteolytic and osteoblastic lesions was not significant (P = .2). The mixed-pattern lesions had higher SUVmax (7.33 ± 2.75, when compared with the osteolytic and osteoblastic lesions; P1 = 0.013 and P2 = 0.0007, respectively), but the [18F]FDG intensity within these lesions seemed heterogeneous, with some parts showing intense uptake and others showing lower or even no increased [18F]FDG uptake despite the presence of morphologic changes on CT. The 17 lesions diagnosed as bone metastases without corresponding CT morphologic changes also had high [18F]FDG uptake, with a mean SUVmax of 7.17 ± 3.12 (P1 = 0.003 and P2 = 0.0002).
It is noteworthy that a significant percentage of the pure osteolytic and osteoblastic lesions seemed smaller than the mixed-pattern and CT-negative lesions, and this might have some impact on the [18F]FDG uptake intensity difference owing to the partial volume effect.27 In this study, 38% (23 of 72) of the [18F]FDG-avid osteolytic lesions and 60% (15 of 25) of the [18F]FDG-avid osteoblastic lesions were smaller than 20 mm (mean, 14.3 mm), whereas all of the mixed-pattern lesions were larger than 20 mm (mean, 34.3 mm; P = .043). Most of the CT-positive but [18F]FDG-negative lesions were found in patients who had received previous systemic treatment (Table 2). For the seven patients who had not, the [18F]FDG avidity rates were 96.4% (27 of 28 lesions) for osteolytic lesions and 94.1% (16 of 17 lesions) for osteoblastic lesions; there was no mixed-pattern lesion in this group of patients (Table 2). Of the 146 metastases identified on [18F]FDG-PET/CT, bone scan (performed within 5 weeks of baseline [18F]FDG-PET/CT) detected only 108 metastases, and most of them remained positive on follow-up bone scans. Interestingly, five [18F]FDG-avid but CT-negative lesions demonstrated increased avidity on bone scan and four more lesions in regions not covered by [18F]FDG-PET/CT were also detected (skull, two; midfemur, one; proximal-tibia, one).
Changes in [18F]FDG Uptake and Gradual CT Morphologic Changes in Bone Metastases After Anticancer Therapy
Of the 25 [18F]FDG-avid osteoblastic lesions, 13 (52%) became [18F]FDG negative after therapy, but 12 (48%) remained [18F]FDG positive and increased in size on CT. This is illustrated in Figure 3, in which the [18F]FDG uptake and the corresponding CT morphologic changes of an osteoblastic lesion in the fifth lumbar vertebra are shown on sequential [18F]FDG-PET/CT images during a period of 18 months.
Five of the 11 [18F]FDG-avid mixed-pattern lesions remained [18F]FDG avid after treatment, with heterogeneous intratumoral [18F]FDG uptake and morphological changes on CT. All 17 initially [18F]FDG-avid but CT-negative lesions became [18F]FDG negative after therapy; nine of them became clearly osteoblastic on CT, as shown in Appendix Figure A1 (online only).
[18F]FDG Uptake Features and Patient Prognosis
In this study, we investigated the relationship between the [18F]FDG uptake and the radiographic morphology changes of bone metastases after anticancer treatment. Our findings suggest that [18F]FDG uptake reflects the tumor activity of bone metastases in breast cancer, independent of the morphologic characteristics. In contrast, the radiographic changes vary greatly among individual patients and do not seem to correlate with the presence of active tumor. This study also shows that sequential [18F]FDG-PET/CT can provide vital information in monitoring the response of bone metastases to therapy. By monitoring the [18F]FDG uptake changes of 146 individual bone metastases together with corresponding CT appearances, we have been able to reveal the heterogeneous nature of bone metastases. Of the 25 patients investigated, 18 presented with a mixture of osteolytic, osteoblastic, mixed-pattern, or CT-negative lesions on CT before additional treatment, whereas only six patients presented with osteolytic lesions only. These lesions showed a wide range of [18F]FDG uptake intensity. After treatment, 76.4% of [18F]FDG-avid lesions became [18F]FDG negative; however, most of them remained abnormal on CT, with predominantly osteoblastic appearances, and most also remained positive on bone scan. Normal bone is subject to continuous remodeling through the coordinated activity of osteoclasts and osteoblasts.7,8 The classification of bone metastases as osteolytic or osteoblastic actually represents two extremes of a continuum of dysregulated bone remodeling. It is reported that the majority of patients with breast cancer have predominantly osteolytic lesions, whereas approximately 15% to 20% of them have predominantly osteoblastic lesions.7 Breast cancer cells are understood to produce cellular factors that directly or indirectly induce the formation of osteoclasts, but suppress the osteoblast activity.7,28-31 In turn, bone resorption by osteoclasts releases growth factors from the bone matrix that stimulate tumor growth.7,28-31 Such a feedback has been observed in animal experiments in which treatment of myeloma in mice with agents that block bone resorption but have no direct effect on tumor growth not only inhibits the formation of osteoclasts but also decreases the tumor burden.32 By monitoring bone metastases with sequential [18F]FDG-PET/CT imaging, we have observed that the responding osteolytic or CT-negative lesions gradually became osteoblastic. This suggests the possible existence of a reversal of the above-described feedback: in eradicating tumor cells, effective anticancer therapy shifts the balance to favor osteoblast activity and bone formation. The mechanisms of osteoblastic metastasis remain unknown. It can be postulated that tumor cells produce factors stimulating the activity of osteoblasts.7 In this study, two patients who received no previous systemic therapy presented with predominately osteoblastic metastases that were all [18F]FDG avid, and both patients died with progressive metastases. As illustrated in Figure 3, when osteoblastic metastases progressed, while remaining [18F]FDG positive, the metastases indeed became more osteoblastic on CT and larger in size. However, the coexistence of progressive osteolytic and osteoblastic metastases in some patients in this study suggests the complexity of the mechanisms regulating the osteoclast/osteoblast balance in bone metastases. Most previous [18F]FDG-PET studies have focused mainly on evaluating the sensitivity of [18F]FDG imaging in detecting bone metastases.4,5,18-20,33-35 In such cases, the [18F]FDG-PET sensitivity was calculated against other imaging findings, mostly from bone scans, which could not differentiate post-treatment bony changes from active bone metastases. In addition, these studies included patients with varied treatment backgrounds. Without sufficient follow-up data, these studies could not elucidate the relationship between the temporal changes in [18F]FDG uptake and the heterogeneous radiographic appearances of bone metastases. Therefore, conflicting results have been reported, with [18F]FDG-PET sensitivity ranging widely.4,5,35 Notably, recent studies have suggested that serial [18F]FDG-PET is useful in monitoring bone metastasis response to anticancer therapy, but unlike our study, these reports do not include radiographic data of the bone lesions.36,37 It has been reported that osteolytic metastases have significantly higher [18F]FDG uptake than osteoblastic lesions, with a hypothesis that osteolytic lesions contain higher tumor cellularity.18,20 However, in these studies a considerable percentage of the osteoblastic lesions were [18F]FDG negative, which would inevitably have lowered the mean SUV of osteoblastic lesions. We have demonstrated that [18F]FDG-negative lesions, most of which are osteoblastic, are likely to represent post-treatment osteoblastic change rather than active tumor. Therefore, when the [18F]FDG uptake intensity was analyzed in this study, only the [18F]FDG-avid lesions were included. Although the mean SUVmax of osteolytic lesions seems higher, this difference is not significant. Instead, the SUVmax seems more related to the size of the lesion, with larger lesions more likely to have a higher SUVmax, as shown in Figure 1, probably owing to the partial volume effect.27,38 However, unlike the study performed by Cook et al,18 when the SUVmax was measured in this study, partial volume effects were not corrected because this approach is more concordant with clinical practice.27 We found that the presence of persistently [18F]FDG-avid lesions correlated with poorer prognosis. We also found that osteoblastic lesions that were [18F]FDG avid seem more resistant to treatment. Our results initially seem to conflict with the observations by Cook et al18 that patients with osteoblastic or mixed-pattern disease have a better prognosis. As mentioned, however, in the study by Cook et al, all of the osteoblastic lesions were included, and a large percentage of them were not [18F]FDG avid. Our data suggest that this type of lesion is in fact more likely to represent post-treatment change rather than active tumor, and assessment of persistently [18F]FDG-avid lesions seems more useful in evaluating the effectiveness of anticancer therapy. The availability of corresponding high-resolution CT images in hybrid PET/CT improves the sensitivity and specificity of [18F]FDG-PET imaging,33,35,39,40 and the interobserver variability in this study has been minimal. With only [18F]FDG-PET images, it is usually difficult to identify small lesions and localize them accurately to the skeleton because of the limited spatial resolution of the technique.33,35 In this study, we were able to identify 38 bone metastases smaller than 20 mm, with the smallest lesion measuring 4.8 mm (maximum long axis). When the corresponding bone scans were reviewed, even with knowledge of the [18F]FDG-PET/CT findings, 26 of these lesions were still either invisible or nonspecific on bone scan. However, we have found that the diagnosis of bone metastases showing no CT morphologic change (CT negative) poses a challenge, and there were three preconsensus discordant lesions in this category (one excluded on consensus). It has been reported that such metastases could account for a much higher percentage in certain malignancies, such as lymphoma.33 This reflects the existence of intrinsic limitations of [18F]FDG-PET/CT imaging. In conclusion, 146 bone deposits from 25 patients with breast carcinoma were followed up for a median period of 23 months. Appearances on [18F]FDG-PET and CT images were investigated and compared. [18F]FDG-PET/CT hybrid imaging was found to better reflect tumor activity of bone metastases. Prospective trials to confirm and expand our initial observations in bone metastases from breast cancer, and to investigate whether these observations apply to other cancers, are clearly warranted.
The author(s) indicated no potential conflicts of interest.
Conception and design: Yong Du, Peter J. Ell Administrative support: Ian Cullum, Peter J. Ell Provision of study materials or patients: Yong Du, Ian Cullum, Peter J. Ell Collection and assembly of data: Yong Du, Peter J. Ell Data analysis and interpretation: Yong Du, Ian Cullum, Tim M. Illidge, Peter J. Ell Manuscript writing: Yong Du, Tim M. Illidge, Peter J. Ell Final approval of manuscript: Yong Du, Ian Cullum, Tim M. Illidge, Peter J. Ell
Supported by the United Kingdom Department of Health's National Institute of Health Research Biomedical Research Centres funding scheme (to University College London Hospitals/University College London). Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article. published online ahead of print at www.jco.org on June 25, 2007.
1. Juweid ME, Cheson BD: Positron-emission tomography and assessment of cancer therapy. N Engl J Med 354:496-507, 2006 2. von Schulthess GK, Steinert HC, Hany TF: Integrated PET/CT: Current applications and future directions. Radiology 238:405-422, 2006 3. Ell PJ: The contribution of PET/CT to improved patient management. Br J Radiol 79:32-36, 2006 4. Fogelman I: Osteoblastic bone metastases in breast cancer: Is not seeing believing? Eur J Nucl Med Mol Imaging 32:1250-1252, 2005[CrossRef][Medline] 5. Fogelman I, Cook G, Israel O, et al: Positron emission tomography and bone metastases. Semin Nucl Med 35:135-142, 2005[CrossRef][Medline] 6. Williams HT, Smith S: FDG PET and SPECT of bone metastases in breast cancer. AJR Am J Roentgenol 185:1651-1652, 2005 7. Roodman GD: Mechanisms of bone metastasis. N Engl J Med 350:1655-1664, 2004 8. Nielsen OS, Munro AJ, Tannock IF: Bone metastases: Pathophysiology and management policy. J Clin Oncol 9:509-524, 1991[Abstract] 9. Coleman RE: Management of bone metastases. Oncologist 5:463-470, 2000 10. Hortobagyi GN: Progress in the management of bone metastases: One continent at a time? J Clin Oncol 23:3299-3301, 2005 11. Palmedo H, Manka-Waluch A, Albers P, et al: Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: Randomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidenediphosphonate. J Clin Oncol 21:2869-2875, 2003 12. Hortobagyi GN, Theriault RL, Porter L, et al: Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases: Protocol 19 Aredia Breast Cancer Study Group. N Engl J Med 335:1785-1791, 1996 13. Hortobagyi GN: Novel approaches to the management of bone metastases in patients with breast cancer. Semin Oncol 29:134-144, 2002 (3 suppl 11)[Medline] 14. Gainford MC, Dranitsaris G, Clemons M: Systemic treatment of bone metastases from breast cancer: Is it all that it's cracked up to be? J Clin Oncol 23:4802-4803, 2005 15. Hamaoka T, Madewell JE, Podoloff DA, et al: Bone imaging in metastatic breast cancer. J Clin Oncol 22:2942-2953, 2004 16. Langsteger W, Heinisch M, Fogelman I: The role of fluorodeoxyglucose, 18F-dihydroxyphenylalanine, 18F-choline, and 18F-fluoride in bone imaging with emphasis on prostate and breast. Semin Nucl Med 36:73-92, 2006[CrossRef][Medline] 17. Therasse P, Arbuck SG, Eisenhauer EA, et al: New guidelines to evaluate the response to treatment in solid tumors: European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205-216, 2000 18. Cook GJ, Houston S, Rubens R, et al: Detection of bone metastases in breast cancer by 18FDG PET: Differing metabolic activity in osteoblastic and osteolytic lesions. J Clin Oncol 16:3375-3379, 1998[Abstract] 19. Uematsu T, Yuen S, Yukisawa S, et al: Comparison of FDG PET and SPECT for detection of bone metastases in breast cancer. AJR Am J Roentgenol 184:1266-1273, 2005 20. Nakai T, Okuyama C, Kubota T, et al: Pitfalls of FDG-PET for the diagnosis of osteoblastic bone metastases in patients with breast cancer. Eur J Nucl Med Mol Imaging 32:1253-1258, 2005[CrossRef][Medline] 21. Abe K, Sasaki M, Kuwabara Y, et al: Comparison of 18FDG-PET with 99mTc-HMDP scintigraphy for the detection of bone metastases in patients with breast cancer. Ann Nucl Med 19:573-579, 2005[Medline] 22. An YS, Yoon JK, Lee MH, et al: False negative F-18 FDG PET/CT in nonsmall cell lung cancer bone metastases. Clin Nucl Med 30:203-204, 2005[CrossRef][Medline] 23. Israel O, Goldberg A, Nachtigal A, et al: FDG-PET and CT patterns of bone metastases and their relationship to previously administered anti-cancer therapy. Eur J Nucl Med Mol Imaging 33:1280-1284, 2006[CrossRef][Medline] 24. Sugawara Y, Zasadny KR, Neuhoff AW, et al: Reevaluation of the standardized uptake value for FDG: Variations with body weight and methods for correction. Radiology 213:521-525, 1999 25. Bland JM, Altman DG: Survival probabilities (the Kaplan-Meier method). BMJ 317:1572, 1998 26. Bland JM, Altman DG: The logrank test. BMJ 328:1073, 2004 27. Shankar LK, Hoffman JM, Bacharach S, et al: Consensus recommendations for the use of 18F-FDG PET as an indicator of therapeutic response in patients in National Cancer Institute Trials. J Nucl Med 47:1059-1066, 2006 28. Käkönen SM, Mundy GR: Mechanisms of osteolytic bone metastases in breast carcinoma. Cancer 97:834-839, 2003 (3 suppl)[CrossRef][Medline] 29. Hunt NC, Fujikawa Y, Sabokbar A, et al: Cellular mechanisms of bone resorption in breast carcinoma. Br J Cancer 85:78-84, 2001[CrossRef][Medline] 30. Roodman GD: Biology of osteoclast activation in cancer. J Clin Oncol 19:3562-3571, 2001 31. Mastro AM, Gay CV, Welch DR, et al: Breast cancer cells induce osteoblast apoptosis: A possible contributor to bone degradation. J Cell Biochem 91:265-276, 2004[CrossRef][Medline] 32. Croucher PI, Shipman CM, Lippitt J, et al: Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma. Blood 98:3534-3540, 2001 33. Nakamoto Y, Cohade C, Tatsumi M, et al: CT appearance of bone metastases detected with FDG PET as part of the same PET/CT examination. Radiology 237:627-634, 2005 34. Schmidt GP, Schoenberg SO, Schmid R, et al: Screening for bone metastases: Whole-body MRI using a 32-channel system versus dual-modality PET-CT. Eur Radiol 17:939-949, 2007[CrossRef][Medline] 35. Metser U, Lerman H, Blank A, et al: Malignant involvement of the spine: Assessment by 18F-FDG PET/CT. J Nucl Med 45:279-284, 2004 36. Stafford SE, Gralow JR, Schubert EK, et al: Use of serial FDG PET to measure the response of bone-dominant breast cancer to therapy. Acad Radiol 9:913-921, 2002[CrossRef][Medline] 37. Specht JM, Tam SL, Kurland BF, et al: Serial 2-[(18)F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) to monitor treatment of bone-dominant metastatic breast cancer predicts time to progression (TTP). Breast Cancer Res Treat [epub ahead of print on February 1, 2007] 38. Miller TR, Wallis JW, Grothe RA Jr: Design and use of PET tomographs: The effect of slice spacing. J Nucl Med 31:1732-1739, 1990 39. Syed R, Bomanji JB, Nagabhushan N, et al: Impact of combined (18)F-FDG PET/CT in head and neck tumours. Br J Cancer 92:1046-1050, 2005[CrossRef][Medline] 40. Taira AV, Herfkens RJ, Gambhir SS, et al: Detection of bone metastases: Assessment of integrated FDG PET/CT imaging. Radiology 243:204-211, 2007 Submitted February 14, 2007; accepted May 10, 2007.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
TOP
ABSTRACT
INTRODUCTION
). (B) Three-month, (C) 7-month, and (D) 24-month follow-up studies show the gradual and long-lasting osteoblastic change. Apart from multiple [18F]FDG-negative osteoblastic lesions, this patient is clinically well at 26-month follow-up.
