Nuclear Medicine and Molecular Imaging • Original Research Ulaner et al. FDG PET/CT and MDP Bone Scan in Ewing Sarcoma
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Nuclear Medicine and Molecular Imaging Original Research
Is Methylene Diphosphonate Bone Scan Necessary for Initial Staging of Ewing Sarcoma if 18F-FDG PET/ CT Is Performed? Gary A. Ulaner 1,2 Heather Magnan 3,4 John H. Healey 5,6 Wolfgang A. Weber1,2 Paul A. Meyers 3,4 Ulaner GA, Magnan H, Healey JH, Weber WA, Meyers PA
Keywords: Ewing sarcoma, FDG PET/CT, MDP bone scan, metastases, staging DOI:10.2214/AJR.13.11239 Received May 15, 2013; accepted after revision August 24, 2013. G. A. Ulaner received support from a Susan G. Komen for the Cure Career Catalyst Research Grant (KG110441). 1
Department of Radiology, Memorial Sloan-Kettering Cancer Center, 430 E 67th St, New York, NY. Address correspondence to G. A. Ulaner ([email protected]). 2 Department of Radiology, Weill Cornell Medical College, New York, NY. 3 Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY. 4 Department of Pediatrics, Weill Cornell Medical College, New York, NY. 5 Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY. 6 Department of Surgery, Weill Cornell Medical College, New York, NY.
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OBJECTIVE. The purpose of this study was to determine whether methylene diphosphonate (MDP) bone scans are necessary during initial staging in patients with Ewing sarcoma (ES) in whom 18F-FDG PET/CT is performed. MATERIALS AND METHODS. A retrospective review was performed of patients who underwent FDG PET/CT and MDP bone scan before treatment of newly diagnosed ES from January 2004 to November 2012. Studies were reviewed to document suspected primary and metastatic malignancy. Pathology and imaging follow-up were used to determine the presence or absence of disease at suspected sites. RESULTS. Sixty patients were identified in whom FDG PET/CT and MDP bone scans were performed before treatment of newly diagnosed ES. Forty-four primary malignancies had a lytic CT appearance, three were sclerotic, and 13 involved only soft tissue. In 11 of 12 patients with osseous metastases, these were detected on PET/CT, with the one false-negative occurring in a sclerotic primary tumor; in nine of 12 patients with osseous metastases, these were detected on MDP bone scan, with the three false-negatives occurring in patients with lytic primary tumors. Only one of 13 patients with a soft-tissue primary malignancy had bone metastases on both bone scan and PET/CT. PET/CT also showed that eight patients had lung metastases and three patients had lymph node metastases, which were not evident on MDP bone scan. CONCLUSION. When ES is lytic, MDP bone scan does not add to staging performed by FDG PET/CT; thus, MDP bone scanning may be omitted. However, when ES is sclerotic, MDP bone scan may detect osseous metastases not detected by FDG PET/CT.
E
wing sarcoma (ES) is an aggressive small round blue cell malignancy with distinctive histologic and molecular characteristics [1]. Approximately 25% of patients with ES have detectable metastases at diagnosis, most commonly in lung and bone [1–4]. Staging of the primary Ewing sarcoma and metastases is critical for identifying target lesions for therapy, planning surgery, and determining the course of chemotherapy [5]. Medical imaging plays a vital role in the staging of newly diagnosed ES. Imaging of the primary site includes radiography and MRI. Primary ES has a variable appearance, usually lytic, but it may be predominantly or even entirely sclerotic [6]. Imaging for distant metastases commonly includes chest CT, 99mTc–methylene diphosphonate (MDP) bone scan, 18F-FDG PET, or a combination thereof. No standardized paradigms exist for
choosing imaging modalities for staging, although there are published guidelines. The 2012 National Comprehensive Cancer Network guidelines suggest PET or bone scan (or both) for initial staging [7]. The Children’s Oncology Group Bone Tumor Committee suggests chest CT and MDP bone scan and recommends FDG PET, particularly if the primary bone tumor is not visualized on bone scan [8]. Staging by imaging is complemented by bone marrow aspirate or biopsy [1]. Multiple studies have evaluated FDG PET for staging of ES and other pediatric sarcomas [5, 9–14]. FDG PET has been found to be superior to MDP bone scan and CT for the detection of soft-tissue and osseous metastases [5, 9, 10, 12, 15]. More recent studies have shown that the combined metabolic and anatomic detail obtained from FDG PET/CT is significantly more sensitive and specific
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Ulaner et al. for staging of ES than FDG PET alone [14, 16, 17]. Indeed, PET/CT or CT is substantially more sensitive than PET alone for detection of lung metastases [18, 19]. Given the current success of staging ES by use of combined FDG PET/CT, we sought to determine whether MDP bone scan was necessary for staging in patients with ES who were undergoing FDG PET/CT. Materials and Methods This retrospective study was performed after receiving Memorial Sloan Kettering Cancer Center (MSKCC) institutional review board approval. MSKCC databases were used to identify patients who underwent both FDG PET/CT and MDP bone scan within 3 weeks of each other and before treatment of newly diagnosed ES, from January 2004 to November 2012. Medical records were reviewed to document patient age and pathologic results of biopsy or surgery. A nuclear radiologist, with greater than 7 years of experience interpreting FDG PET/CT and MDP bone scans, documented site and characteristics of the primary malignancy, as well as presence of lung, osseous, and soft-tissue metastases. FDG PET/CT and MDP bone scans were interpreted on separate days to reduce bias. Each examination was interpreted individually, without referencing the report or images of the other examination. Specific standardized uptake value cutoffs were not used to define malignancy on FDG PET/ CT studies. The presence of metastases in an organ system was documented, rather than the number of metastatic lesions. Pathology and imaging follow-up for up to 2 years after initial staging were used to determine the presence or absence of malignancy at suspected sites. A case was deemed as discordant for osseous malignancy when FDG PET/CT showed osseous malignancy but the findings on MDP bone scan were benign, or vice versa. Only one discordant case of osseous malignancy used follow-up imaging to determine malignancy; the remaining discordant cases of osseous malignancy were confirmed by pathology. The radiologist documenting FDG PET/CT and bone scan findings was blinded to pathology and follow-up imaging until all initial study results were recorded. The PET/CT examinations were performed according to MSKCC clinical protocols on hybrid PET/CT scanners approximately 60 minutes after IV administration of 12–15 mCi of FDG. At our institution, FDG PET/CT for ES—as well as for some other malignancies, such as melanoma—is performed from the skull to the feet. Patients fast for at least 6 hours, and finger-stick blood glucose levels were less than 200 mg/dL before injection. Spiral
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CT was performed for attenuation correction at 60 mAs and 120–140 kVp, with a 5-mm slice thickness. PET was performed at 3–5 minutes per bed position. IV contrast material was not administered for FDG PET/CT scans. The bone scans were performed according to MSKCC clinical protocols on six SPECT and SPECT/CT gamma cameras including acquisition of planar images from the skull to the feet approximately 2–3 hours after administration of 25 mCi of MDP. On five of the more recent bone scan studies, SPECT/CT images were acquired if needed for clarification of planar imaging findings. No discordant case of osseous malignancy involved SPECT or SPECT/CT for the bone scan.
Results From MSKCC databases, 60 patients were identified who had undergone both FDG PET/CT and MDP bone scan before treatment of newly diagnosed ES. In 37 patients, bone scan was performed before PET/CT; in 10 patients, PET/CT was performed before bone scan; and in 13 patients, both studies were performed on the same day. The median age of patients was 20 years (age range, 6–38 years). All patients had pathology results documenting the primary ES malignancy. Of the 60 patients with ES, 47 had a primary malignancy with osseous involvement, whereas 13 had a primary malignancy involving soft tissues only. Of the 47 patients with an osseous primary tumor, 44 had a lytic or predominantly lytic CT abnormality, and only three had a sclerotic lesion. Nineteen patients had metastatic disease at the time of diagnosis: 12 had osseous metastases, eight had lung metastases, and three had lymph node metastases. Four patients had more than one organ site of metastases: three had bone and lung metastases, and one had lung and lymph node metastases. Two patients had FDG-avid venous thrombi on FDG PET/CT. The characteristics of primary and metastatic disease, as obtained from review of FDG PET/CT and bone scan studies, are summarized in Table 1. Bone scan detected osseous metastases in nine of the 12 patients who had osseous metastases. The three patients whose osseous metastases were seen on FDG PET/CT but not on bone scan all had lytic primary tumors. Of these three patients, one had lytic metastases, and in the other two, metastases were only apparent on FDG PET (i.e., without abnormal findings on CT). All three discordant cases had pathologic confirmation of osseous malignancy, including pathologic
TABLE 1: Characteristics of Primary Ewing Sarcoma (ES) and Metastatic Disease Characteristic
N
Patients with primary ES by location
60
Osseous
47
Skull or jaw (or both)
4
Thorax
13
Scapula
6
Clavicle
1
Rib
6
Spine
6
Pelvis
12
Upper extremity
4
Humerus
3
Radius
1
Lower extremity
8
Femur
5
Tibia
1
Fibula
2
Soft tissue
13
Thorax
6
Pelvis
2
Lower extremity
5
CT appearance of osseous primary ES
47
Lytic or predominantly lytic
44
Sclerotic
3
Patients with metastases at diagnosisa
19
Osseous
12
Lung
8
Lymph node
3
Note—Data are number of patients in each group. aSome patients had metastases to more than one organ site at diagnosis.
findings after en bloc resection in one patient with humeral metastases and after biopsy in the other two patients. An example from a patient with osseous metastases missed on bone scan is given in Figure 1. In this patient, the osseous metastases were apparent only on FDG PET (i.e., without abnormal findings on CT). There was one false-positive on bone scan, a skull focus that was characterized as a stable benign osteoma on subsequent head CT examinations. FDG PET/CT detected osseous metastases in 11 of the 12 patients who had osse-
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FDG PET/CT and MDP Bone Scan in Ewing Sarcoma right thigh soft-tissue primary ES, is shown in Figure 3. In one patient, FDG-avid lymph nodes considered to be malignant on the basis of PET/CT were biopsy proven to be a false-positive due to granulomatous lymphadenitis. Two patients had venous thrombi detected as FDG-avid lesions on FDG PET/ CT. One of these patients also had an FDGavid thrombus in the heart, substantiated by cardiac MRI (Fig. 4). Pathology was not available to determine if these were benign or malignant thrombi. Overall, ES with lytic or sclerotic primary tumors were most likely to metastasize to bone and lung, as shown in previous studies. ES with soft-tissue-only primary tumors had a higher propensity to metastasize to the lymph nodes and cause venous thrombi. A summary of metastatic sites according to the CT appearance of the primary tumor is given in Table 3.
ous metastases. The one patient with osseous metastases seen on bone scan but not on FDG PET/CT had a sclerotic primary tumor (Fig. 2). The diagnosis of osseous metastasis in this discordant case was confirmed on follow-up imaging. After chemotherapy, the MDP-avid bone foci resolved, and the sites of MDP avidity became sclerotic on CT, consistent with healing osseous metastases. It is unlikely that the combination of resolved MDP avidity and increased osseous sclerosis could be due to a benign cause. This patient subsequently experienced a relapse with additional osseous metastases. A summary of osseous metastatic disease as found on FDG PET/CT and MDP bone scan is shown in Table 2. FDG PET/CT was also valuable in showing soft-tissue malignancy. Of the 13 primary malignancies without osseous involvement on CT, all 13 were visualized on FDG PET/CT, but only five were evident on bone scan as MDP avidity in the bone adjacent to the soft-tissue mass. This did not affect staging because all 13 malignancies were visualized on MRI performed for local staging. Eight patients’ lung metastases were visualized with FDG PET/CT, none of which were evident on bone scan. Again, staging was not affected because the lung metastases in all eight patients were seen on staging chest CT. Of note, three patients had lymph node metastases seen on FDG PET/CT, none of which were evident on bone scan. In two of these three patients, the affected lymph node was less than 1 cm in short axis, and detection on PET/CT changed staging in these patients. An example of a biopsy-proven lymph node metastasis, in a patient with a
Discussion The best imaging strategy for staging newly diagnosed ES has not been established. Recent studies suggest the superiority of FDG PET/CT over MDP bone scan for detection of ES metastases [13, 14]. We investigated whether MDP bone scan was necessary for the staging of newly diagnosed ES in patients who undergo FDG PET/CT. In 44 patients in whom the primary ES had a lytic appearance on FDG PET/CT, bone scan added no additional staging value. We propose that in these patients, MDP bone scans may be omitted from staging paradigms. Sclerotic ES is rare. The present study includes only three patients with primary scle-
TABLE 2: Osseous Metastatic Disease Detected on 18F-FDG PET/CT and 99mTc–Methylene Diphosphonate (MDP) Bone Scan in 60 Patients With Newly Diagnosed Ewing Sarcoma Parameter
Positive Finding on FDG PET/CT
Positive Finding on MDP Bone Scan
No. of true-positives
11
9
No. of false-positives
0
1
No. of false-negatives
1
3
TABLE 3: Sites of Metastatic Disease Grouped by Appearance of the Primary Ewing Sarcoma on CT CT Appearance of Primary Tumor
Osseous Metastases
Pulmonary Metastases
Nodal Metastases
Venous Thrombi
Lytic (n = 44)
10
5
1
0
Sclerotic (n = 3)
1
1
0
0
Soft tissue only (n = 13)
1
2
2
2
rotic ES. However, in one of these three patients, osseous metastases were detected on MDP bone scan, which were missed on FDG PET/CT. This is analogous to other primary malignancies, where sclerotic osseous metastases may be better appreciated on bone scan than on FDG PET/CT [20]. Primary ES with only a soft-tissue abnormality on CT is less common than primary osseous involvement. The present study includes 13 patients with primary soft-tissue ES. Only one patient from this group had osseous metastases, which were seen on both bone scan and PET/CT. Although the numbers are too small to make conclusions, these patients may be less likely to have osseous metastases at diagnosis than patients with primary osseous ES. They may be more likely to present with nodal metastases and venous thrombi (see Table 3). Before this investigation, both FDG PET/ CT and MDP bone scan were routinely performed at our institution for staging of newly diagnosed ES, and the bone scan was more commonly performed first. Our practice has now evolved to perform FDG PET/CT first. If the primary malignancy is osseous and lytic, then no MDP bone scan is performed. If the primary malignancy is osseous and sclerotic, then MDP bone scan is performed for further staging of potential osseous metastases occult on FDG PET/CT. For primary softtissue ES malignancy, MDP bone scan is still performed, although little data exist to support this. Our proposed algorithm for staging newly diagnosed ES is diagrammed in Figure 5. Lymph node metastases are reported to be rare in ES [21]. Although uncommon in the present study cohort, lymph node metastases were present at time of diagnosis of ES in three patients. In two of these patients, metastases were detected on FDG PET/CT in lymph nodes less than 1 cm in short axis. It is possible that with increased use of FDG PET/CT, the prevalence of detectable lymph node metastases at time of diagnosis of ES may increase, particularly in patients with primary soft-tissue ES. In the present study, gamma imaging of MDP was used for bone scans. In the future, PET using 18F-fluoride may supplant MDP bone scan imaging. The effect of 18F-fluoride PET/CT on the utility of bone scans in newly diagnosed ES is unknown. Similarly, almost all bone scans in the present study were performed only with planar imaging. The effect of standard SPECT or SPECT/CT on bone scans is not known.
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Ulaner et al. The strengths of the present study include its large cohort size, the uniformity of patients with newly diagnosed malignancy, and biopsy proof of all primary disease. ES is a relatively uncommon malignancy, which makes accumulation of cases for a cohort difficult. The large volume of ES cases at MSKCC thus has allowed one of the largest cohorts published. In addition, all patients in this the present study had newly diagnosed ES, not restaging studies. This allowed evaluation of bone scan and PET/CT in the initial staging of ES. The weaknesses of the present study include the retrospective study design and possible selection bias. Retrospective studies introduce inherent biases that are difficult to overcome, including nonstandardized criteria for interpretation of the original studies. There may have been selection bias in the cohort, because not all patients with newly diagnosed ES underwent both PET/CT and bone scan during the defined time period. The present study addresses initial staging of ES, not the role of FDG PET/CT or bone scan on monitoring response to therapy. In summary, prior studies have suggested that FDG PET/CT is superior to MDP bone scan for detection of ES metastases. The present study has shown that this may not be true for ES when the primary malignancy is sclerotic on CT, a less common but encountered ES morphology. This retrospective trial suggests that bone scan may be omitted from the staging of newly diagnosed ES when the primary tumor is lytic on FDG PET/CT. When the primary ES is sclerotic, MDP bone scan may detect osseous metastases that are missed on FDG PET/CT. References 1. Potratz J, Dirksen U, Jürgens H, Craft A. Ewing sarcoma: clinical state-of-the-art. Pediatr Hematol Oncol 2012; 29:1–11 2. Grier HE. The Ewing family of tumors: Ewing’s sarcoma and primitive neuroectodermal tumors. Pediatr Clin North Am 1997; 44:991–1004
3. Paulussen M, Ahrens S, Burdach S, et al.; European Intergroup Cooperative Ewing Sarcoma Studies (EICESS). Primary metastatic (stage IV) Ewing tumor: survival analysis of 171 patients from the EICESS studies. Ann Oncol 1998; 9:275–281 4. Bernstein ML, Devidas M, Lafreniere D, et al. Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children’s Cancer Group Phase II Study 9457—a report from the Children’s Oncology Group. J Clin Oncol 2006; 24:152–159 5. Völker T, Denecke T, Steffen I, et al. Positron emission tomography for staging of pediatric sarcoma patients: results of a prospective multicenter trial. J Clin Oncol 2007; 25:5435–5441 6. Reinus WR, Gehan EA, Gilula LA, Nesbit M. Plain radiographic predictors of survival in treated Ewing’s sarcoma. IESS Committee. Skeletal Radiol 1992; 21:287–291 7. National Comprehensive Cancer Network. Ewing’s sarcoma family of tumors. In: NCCN clinical practice guidelines in oncology (NCCN Guidelines®): bone cancer, version 1.2014. www. nccn.org/professionals/physician_gls/pdf/bone. pdf. Published September 24, 2013. Accessed December 12, 2013 8. Meyer JS, Nadel HR, Marina N, et al. Imaging guidelines for children with Ewing sarcoma and osteosarcoma: a report from the Children’s Oncology Group Bone Tumor Committee. Pediatr Blood Cancer 2008; 51:163–170 9. Györke T, Zajic T, Lange A, et al. Impact of FDG PET for staging of Ewing sarcomas and primitive neuroectodermal tumours. Nucl Med Commun 2006; 27:17–24 10. Furth C, Amthauer H, Denecke T, Ruf J, Henze G, Gutberlet M. Impact of whole-body MRI and FDG-PET on staging and assessment of therapy response in a patient with Ewing sarcoma. Pediatr Blood Cancer 2006; 47:607–611 11. Daldrup-Link HE, Franzius C, Link TM, et al. Whole-body MR imaging for detection of bone metastases in children and young adults: comparison with skeletal scintigraphy and FDG PET. AJR 2001; 177:229–236
12. Franzius C, Sciuk J, Daldrup-Link HE, Jürgens H, Schober O. FDG-PET for detection of osseous metastases from malignant primary bone tumours: comparison with bone scintigraphy. Eur J Nucl Med 2000; 27:1305–1311 13. Walter F, Czernin J, Hall T, et al. Is there a need for dedicated bone imaging in addition to 18F-FDG PET/CT imaging in pediatric sarcoma patients? J Pediatr Hematol Oncol 2012; 34:131–136 14. Treglia G, Salsano M, Stefanelli A, Mattoli MV, Giordano A, Bonomo L. Diagnostic accuracy of 18F-FDG-PET and PET/CT in patients with Ewing sarcoma family tumours: a systematic review and a meta-analysis. Skeletal Radiol 2012; 41:249–256 15. Newman EN, Jones RL, Hawkins DS. An evaluation of [F-18]-fluorodeoxy-d-glucose positron emission tomography, bone scan, and bone marrow aspiration/biopsy as staging investigations in Ewing sarcoma. Pediatr Blood Cancer 2013; 60:1113–1117 16. Gerth HU, Juergens KU, Dirksen U, Gerss J, Schober O, Franzius C. Significant benefit of multimodal imaging: PET/CT compared with PET alone in staging and follow-up of patients with Ewing tumors. J Nucl Med 2007; 48:1932–1939 17. Tateishi U, Yamaguchi U, Seki K, Terauchi T, Arai Y, Kim EE. Bone and soft-tissue sarcoma: preoperative staging with fluorine 18 fluorodeoxyglucose PET/CT and conventional imaging. Radiology 2007; 245:839–847 18. Franzius C, Daldrup-Link HE, Sciuk J, et al. FDG-PET for detection of pulmonary metastases from malignant primary bone tumors: comparison with spiral CT. Ann Oncol 2001; 12:479–486 19. Charest M, Hickeson M, Lisbona R, Novales-Diaz JA, Derbekyan V, Turcotte RE. FDG PET/CT imaging in primary osseous and soft tissue sarcomas: a retrospective review of 212 cases. Eur J Nucl Med Mol Imaging 2009; 36:1944–1951 20. Cook GJ, Houston S, Rubens R, Maisey MN, Fogelman I. Detection of bone metastases in breast cancer by 18FDG PET: differing metabolic activity in osteoblastic and osteolytic lesions. J Clin Oncol 1998; 16:3375–3379 21. Kaste SC. Imaging pediatric bone sarcomas. Radiol Clin North Am 2011; 49:749–765, vi–vii
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FDG PET/CT and MDP Bone Scan in Ewing Sarcoma
A
B
C Fig. 1—32-year-old man with Ewing sarcoma (ES) with bone metastases detected on 18F-FDG PET/CT but not on methylene diphosphonate (MDP) bone scan. A, Posterior and anterior planar bone scan images show abnormal MDP uptake in left scapula representing primary ES (arrows). B, FDG PET/CT maximum intensity projection image shows not only abnormal uptake in left scapula primary ES (arrow) but also multiple osseous metastases (arrowheads) in spine and upper and lower extremities. Primary malignancy was lytic on CT (not shown). C, Axial CT (left) and fused PET/CT (right) images of left humerus show FDG-avid osseous metastasis (arrowhead) slightly misregistered from CT. En bloc resection of left humeral lesion yielded diagnosis of metastatic ES on pathology.
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Ulaner et al.
B
A
C
D
E
Fig. 2—35-year-old woman with Ewing sarcoma (ES). Bone metastases detected on methylene diphosphonate (MDP) bone scan but not on 18F-FDG PET/CT. A, FDG PET/CT maximum intensity projection image shows left clavicular primary ES (arrow). B, Axial CT (left) and fused PET/CT (right) images of left clavicular primary ES show that associated left shoulder soft-tissue mass (arrows) is FDG avid, whereas sclerotic osseous lesion (arrowheads) is not. C, Axial CT (left) and fused PET/CT (right) images of L1 vertebral body show non–FDG-avid mild sclerosis (arrows), considered nonspecific on PET/CT. D, Posterior and anterior planar MDP bone scan images show not only left clavicular primary ES (arrows) but also multiple osseous metastases (arrowheads) in L1 vertebral body, posterior right rib, and right ilium. E, Repeat bone scan after chemotherapy shows resolution of MDP-avid metastases. MDP is seen in right chest wall MediPort catheter (curved arrow).
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FDG PET/CT and MDP Bone Scan in Ewing Sarcoma
F
G Fig. 2 (continued)—35-year-old woman with Ewing sarcoma (ES). Bone metastases detected on methylene diphosphonate (MDP) bone scan but not on 18F-FDG PET/CT. F, Postchemotherapy axial CT (left) and fused PET/CT (right) images show resolution of FDG-avid left shoulder mass (arrows). Non–FDG-avid sclerotic clavicular lesion remains (arrowheads). Physiologic FDG avidity is seen in vocal cords (curved arrow). G, Postchemotherapy axial CT (left) and fused PET/CT (right) images show increased sclerosis of L1 vertebral body (arrow) consistent with healing of osseous metastases. FDG-avid bone marrow repopulation in left aspect of vertebra (arrowhead) is absent in healing metastasis.
Fig. 3—14-year-old girl with primary Ewing sarcoma with pelvic lymph node metastasis detected on 18F-FDG PET/CT. Axial CT (left) and fused PET/CT (right) images of right thigh soft tissues. An FDG-avid lymph node (arrows) in right pelvis is less than 1 cm in short axis and easily overlooked without addition of FDG PET. Lymph node metastasis was subsequently confirmed on biopsy.
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Ulaner et al.
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B
C Fig. 4—Venous thrombus detected on 18F-FDG PET/CT in same patient as in Fig. 3. A, Coronal CT (left) and fused PET/CT (right) images show linear FDG-avid expansion and filling of right femoral vein (arrows) representing venous thrombus. Primary right thigh soft-tissue Ewing sarcoma (arrowheads) is also shown. B, Coronal CT (left) and fused PET/CT (right) images at level of heart show FDG-avid low-attenuation thrombus (arrows) in right ventricle. C, Right ventricle thrombus (arrow) was confirmed on cardiac MRI (inversion recovery T1 with fat saturation).
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FDG PET/CT and MDP Bone Scan in Ewing Sarcoma
Newly diagnosed ES Staging with FDG PET/CT
Primary ES on FDG PET/CT is osseous and lytic No MDP bone scan is performed
Primary ES on FDG PET/CT is osseous and sclerotic
Primary ES on FDG PET/CT is soft tissue (not osseous)
MDP bone scan is added for osseous staging
Fig. 5—Proposed algorithm for staging of newly diagnosed Ewing sarcoma (ES) with 18 F-FDG PET/CT and methylene diphosphonate (MDP) bone scan.
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Nuclear Medicine and Molecular Imaging Original Research
Is Methylene Diphosphonate Bone Scan Necessary for Initial Staging of Ewing Sarcoma if 18F-FDG PET/ CT Is Performed? Gary A. Ulaner 1,2 Heather Magnan 3,4 John H. Healey 5,6 Wolfgang A. Weber1,2 Paul A. Meyers 3,4 Ulaner GA, Magnan H, Healey JH, Weber WA, Meyers PA
Keywords: Ewing sarcoma, FDG PET/CT, MDP bone scan, metastases, staging DOI:10.2214/AJR.13.11239 Received May 15, 2013; accepted after revision August 24, 2013. G. A. Ulaner received support from a Susan G. Komen for the Cure Career Catalyst Research Grant (KG110441). 1
Department of Radiology, Memorial Sloan-Kettering Cancer Center, 430 E 67th St, New York, NY. Address correspondence to G. A. Ulaner ([email protected]). 2 Department of Radiology, Weill Cornell Medical College, New York, NY. 3 Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY. 4 Department of Pediatrics, Weill Cornell Medical College, New York, NY. 5 Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY. 6 Department of Surgery, Weill Cornell Medical College, New York, NY.
AJR 2014; 202:859–867 0361–803X/14/2024–859 © American Roentgen Ray Society
OBJECTIVE. The purpose of this study was to determine whether methylene diphosphonate (MDP) bone scans are necessary during initial staging in patients with Ewing sarcoma (ES) in whom 18F-FDG PET/CT is performed. MATERIALS AND METHODS. A retrospective review was performed of patients who underwent FDG PET/CT and MDP bone scan before treatment of newly diagnosed ES from January 2004 to November 2012. Studies were reviewed to document suspected primary and metastatic malignancy. Pathology and imaging follow-up were used to determine the presence or absence of disease at suspected sites. RESULTS. Sixty patients were identified in whom FDG PET/CT and MDP bone scans were performed before treatment of newly diagnosed ES. Forty-four primary malignancies had a lytic CT appearance, three were sclerotic, and 13 involved only soft tissue. In 11 of 12 patients with osseous metastases, these were detected on PET/CT, with the one false-negative occurring in a sclerotic primary tumor; in nine of 12 patients with osseous metastases, these were detected on MDP bone scan, with the three false-negatives occurring in patients with lytic primary tumors. Only one of 13 patients with a soft-tissue primary malignancy had bone metastases on both bone scan and PET/CT. PET/CT also showed that eight patients had lung metastases and three patients had lymph node metastases, which were not evident on MDP bone scan. CONCLUSION. When ES is lytic, MDP bone scan does not add to staging performed by FDG PET/CT; thus, MDP bone scanning may be omitted. However, when ES is sclerotic, MDP bone scan may detect osseous metastases not detected by FDG PET/CT.
E
wing sarcoma (ES) is an aggressive small round blue cell malignancy with distinctive histologic and molecular characteristics [1]. Approximately 25% of patients with ES have detectable metastases at diagnosis, most commonly in lung and bone [1–4]. Staging of the primary Ewing sarcoma and metastases is critical for identifying target lesions for therapy, planning surgery, and determining the course of chemotherapy [5]. Medical imaging plays a vital role in the staging of newly diagnosed ES. Imaging of the primary site includes radiography and MRI. Primary ES has a variable appearance, usually lytic, but it may be predominantly or even entirely sclerotic [6]. Imaging for distant metastases commonly includes chest CT, 99mTc–methylene diphosphonate (MDP) bone scan, 18F-FDG PET, or a combination thereof. No standardized paradigms exist for
choosing imaging modalities for staging, although there are published guidelines. The 2012 National Comprehensive Cancer Network guidelines suggest PET or bone scan (or both) for initial staging [7]. The Children’s Oncology Group Bone Tumor Committee suggests chest CT and MDP bone scan and recommends FDG PET, particularly if the primary bone tumor is not visualized on bone scan [8]. Staging by imaging is complemented by bone marrow aspirate or biopsy [1]. Multiple studies have evaluated FDG PET for staging of ES and other pediatric sarcomas [5, 9–14]. FDG PET has been found to be superior to MDP bone scan and CT for the detection of soft-tissue and osseous metastases [5, 9, 10, 12, 15]. More recent studies have shown that the combined metabolic and anatomic detail obtained from FDG PET/CT is significantly more sensitive and specific
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Ulaner et al. for staging of ES than FDG PET alone [14, 16, 17]. Indeed, PET/CT or CT is substantially more sensitive than PET alone for detection of lung metastases [18, 19]. Given the current success of staging ES by use of combined FDG PET/CT, we sought to determine whether MDP bone scan was necessary for staging in patients with ES who were undergoing FDG PET/CT. Materials and Methods This retrospective study was performed after receiving Memorial Sloan Kettering Cancer Center (MSKCC) institutional review board approval. MSKCC databases were used to identify patients who underwent both FDG PET/CT and MDP bone scan within 3 weeks of each other and before treatment of newly diagnosed ES, from January 2004 to November 2012. Medical records were reviewed to document patient age and pathologic results of biopsy or surgery. A nuclear radiologist, with greater than 7 years of experience interpreting FDG PET/CT and MDP bone scans, documented site and characteristics of the primary malignancy, as well as presence of lung, osseous, and soft-tissue metastases. FDG PET/CT and MDP bone scans were interpreted on separate days to reduce bias. Each examination was interpreted individually, without referencing the report or images of the other examination. Specific standardized uptake value cutoffs were not used to define malignancy on FDG PET/ CT studies. The presence of metastases in an organ system was documented, rather than the number of metastatic lesions. Pathology and imaging follow-up for up to 2 years after initial staging were used to determine the presence or absence of malignancy at suspected sites. A case was deemed as discordant for osseous malignancy when FDG PET/CT showed osseous malignancy but the findings on MDP bone scan were benign, or vice versa. Only one discordant case of osseous malignancy used follow-up imaging to determine malignancy; the remaining discordant cases of osseous malignancy were confirmed by pathology. The radiologist documenting FDG PET/CT and bone scan findings was blinded to pathology and follow-up imaging until all initial study results were recorded. The PET/CT examinations were performed according to MSKCC clinical protocols on hybrid PET/CT scanners approximately 60 minutes after IV administration of 12–15 mCi of FDG. At our institution, FDG PET/CT for ES—as well as for some other malignancies, such as melanoma—is performed from the skull to the feet. Patients fast for at least 6 hours, and finger-stick blood glucose levels were less than 200 mg/dL before injection. Spiral
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CT was performed for attenuation correction at 60 mAs and 120–140 kVp, with a 5-mm slice thickness. PET was performed at 3–5 minutes per bed position. IV contrast material was not administered for FDG PET/CT scans. The bone scans were performed according to MSKCC clinical protocols on six SPECT and SPECT/CT gamma cameras including acquisition of planar images from the skull to the feet approximately 2–3 hours after administration of 25 mCi of MDP. On five of the more recent bone scan studies, SPECT/CT images were acquired if needed for clarification of planar imaging findings. No discordant case of osseous malignancy involved SPECT or SPECT/CT for the bone scan.
Results From MSKCC databases, 60 patients were identified who had undergone both FDG PET/CT and MDP bone scan before treatment of newly diagnosed ES. In 37 patients, bone scan was performed before PET/CT; in 10 patients, PET/CT was performed before bone scan; and in 13 patients, both studies were performed on the same day. The median age of patients was 20 years (age range, 6–38 years). All patients had pathology results documenting the primary ES malignancy. Of the 60 patients with ES, 47 had a primary malignancy with osseous involvement, whereas 13 had a primary malignancy involving soft tissues only. Of the 47 patients with an osseous primary tumor, 44 had a lytic or predominantly lytic CT abnormality, and only three had a sclerotic lesion. Nineteen patients had metastatic disease at the time of diagnosis: 12 had osseous metastases, eight had lung metastases, and three had lymph node metastases. Four patients had more than one organ site of metastases: three had bone and lung metastases, and one had lung and lymph node metastases. Two patients had FDG-avid venous thrombi on FDG PET/CT. The characteristics of primary and metastatic disease, as obtained from review of FDG PET/CT and bone scan studies, are summarized in Table 1. Bone scan detected osseous metastases in nine of the 12 patients who had osseous metastases. The three patients whose osseous metastases were seen on FDG PET/CT but not on bone scan all had lytic primary tumors. Of these three patients, one had lytic metastases, and in the other two, metastases were only apparent on FDG PET (i.e., without abnormal findings on CT). All three discordant cases had pathologic confirmation of osseous malignancy, including pathologic
TABLE 1: Characteristics of Primary Ewing Sarcoma (ES) and Metastatic Disease Characteristic
N
Patients with primary ES by location
60
Osseous
47
Skull or jaw (or both)
4
Thorax
13
Scapula
6
Clavicle
1
Rib
6
Spine
6
Pelvis
12
Upper extremity
4
Humerus
3
Radius
1
Lower extremity
8
Femur
5
Tibia
1
Fibula
2
Soft tissue
13
Thorax
6
Pelvis
2
Lower extremity
5
CT appearance of osseous primary ES
47
Lytic or predominantly lytic
44
Sclerotic
3
Patients with metastases at diagnosisa
19
Osseous
12
Lung
8
Lymph node
3
Note—Data are number of patients in each group. aSome patients had metastases to more than one organ site at diagnosis.
findings after en bloc resection in one patient with humeral metastases and after biopsy in the other two patients. An example from a patient with osseous metastases missed on bone scan is given in Figure 1. In this patient, the osseous metastases were apparent only on FDG PET (i.e., without abnormal findings on CT). There was one false-positive on bone scan, a skull focus that was characterized as a stable benign osteoma on subsequent head CT examinations. FDG PET/CT detected osseous metastases in 11 of the 12 patients who had osse-
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FDG PET/CT and MDP Bone Scan in Ewing Sarcoma right thigh soft-tissue primary ES, is shown in Figure 3. In one patient, FDG-avid lymph nodes considered to be malignant on the basis of PET/CT were biopsy proven to be a false-positive due to granulomatous lymphadenitis. Two patients had venous thrombi detected as FDG-avid lesions on FDG PET/ CT. One of these patients also had an FDGavid thrombus in the heart, substantiated by cardiac MRI (Fig. 4). Pathology was not available to determine if these were benign or malignant thrombi. Overall, ES with lytic or sclerotic primary tumors were most likely to metastasize to bone and lung, as shown in previous studies. ES with soft-tissue-only primary tumors had a higher propensity to metastasize to the lymph nodes and cause venous thrombi. A summary of metastatic sites according to the CT appearance of the primary tumor is given in Table 3.
ous metastases. The one patient with osseous metastases seen on bone scan but not on FDG PET/CT had a sclerotic primary tumor (Fig. 2). The diagnosis of osseous metastasis in this discordant case was confirmed on follow-up imaging. After chemotherapy, the MDP-avid bone foci resolved, and the sites of MDP avidity became sclerotic on CT, consistent with healing osseous metastases. It is unlikely that the combination of resolved MDP avidity and increased osseous sclerosis could be due to a benign cause. This patient subsequently experienced a relapse with additional osseous metastases. A summary of osseous metastatic disease as found on FDG PET/CT and MDP bone scan is shown in Table 2. FDG PET/CT was also valuable in showing soft-tissue malignancy. Of the 13 primary malignancies without osseous involvement on CT, all 13 were visualized on FDG PET/CT, but only five were evident on bone scan as MDP avidity in the bone adjacent to the soft-tissue mass. This did not affect staging because all 13 malignancies were visualized on MRI performed for local staging. Eight patients’ lung metastases were visualized with FDG PET/CT, none of which were evident on bone scan. Again, staging was not affected because the lung metastases in all eight patients were seen on staging chest CT. Of note, three patients had lymph node metastases seen on FDG PET/CT, none of which were evident on bone scan. In two of these three patients, the affected lymph node was less than 1 cm in short axis, and detection on PET/CT changed staging in these patients. An example of a biopsy-proven lymph node metastasis, in a patient with a
Discussion The best imaging strategy for staging newly diagnosed ES has not been established. Recent studies suggest the superiority of FDG PET/CT over MDP bone scan for detection of ES metastases [13, 14]. We investigated whether MDP bone scan was necessary for the staging of newly diagnosed ES in patients who undergo FDG PET/CT. In 44 patients in whom the primary ES had a lytic appearance on FDG PET/CT, bone scan added no additional staging value. We propose that in these patients, MDP bone scans may be omitted from staging paradigms. Sclerotic ES is rare. The present study includes only three patients with primary scle-
TABLE 2: Osseous Metastatic Disease Detected on 18F-FDG PET/CT and 99mTc–Methylene Diphosphonate (MDP) Bone Scan in 60 Patients With Newly Diagnosed Ewing Sarcoma Parameter
Positive Finding on FDG PET/CT
Positive Finding on MDP Bone Scan
No. of true-positives
11
9
No. of false-positives
0
1
No. of false-negatives
1
3
TABLE 3: Sites of Metastatic Disease Grouped by Appearance of the Primary Ewing Sarcoma on CT CT Appearance of Primary Tumor
Osseous Metastases
Pulmonary Metastases
Nodal Metastases
Venous Thrombi
Lytic (n = 44)
10
5
1
0
Sclerotic (n = 3)
1
1
0
0
Soft tissue only (n = 13)
1
2
2
2
rotic ES. However, in one of these three patients, osseous metastases were detected on MDP bone scan, which were missed on FDG PET/CT. This is analogous to other primary malignancies, where sclerotic osseous metastases may be better appreciated on bone scan than on FDG PET/CT [20]. Primary ES with only a soft-tissue abnormality on CT is less common than primary osseous involvement. The present study includes 13 patients with primary soft-tissue ES. Only one patient from this group had osseous metastases, which were seen on both bone scan and PET/CT. Although the numbers are too small to make conclusions, these patients may be less likely to have osseous metastases at diagnosis than patients with primary osseous ES. They may be more likely to present with nodal metastases and venous thrombi (see Table 3). Before this investigation, both FDG PET/ CT and MDP bone scan were routinely performed at our institution for staging of newly diagnosed ES, and the bone scan was more commonly performed first. Our practice has now evolved to perform FDG PET/CT first. If the primary malignancy is osseous and lytic, then no MDP bone scan is performed. If the primary malignancy is osseous and sclerotic, then MDP bone scan is performed for further staging of potential osseous metastases occult on FDG PET/CT. For primary softtissue ES malignancy, MDP bone scan is still performed, although little data exist to support this. Our proposed algorithm for staging newly diagnosed ES is diagrammed in Figure 5. Lymph node metastases are reported to be rare in ES [21]. Although uncommon in the present study cohort, lymph node metastases were present at time of diagnosis of ES in three patients. In two of these patients, metastases were detected on FDG PET/CT in lymph nodes less than 1 cm in short axis. It is possible that with increased use of FDG PET/CT, the prevalence of detectable lymph node metastases at time of diagnosis of ES may increase, particularly in patients with primary soft-tissue ES. In the present study, gamma imaging of MDP was used for bone scans. In the future, PET using 18F-fluoride may supplant MDP bone scan imaging. The effect of 18F-fluoride PET/CT on the utility of bone scans in newly diagnosed ES is unknown. Similarly, almost all bone scans in the present study were performed only with planar imaging. The effect of standard SPECT or SPECT/CT on bone scans is not known.
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Ulaner et al. The strengths of the present study include its large cohort size, the uniformity of patients with newly diagnosed malignancy, and biopsy proof of all primary disease. ES is a relatively uncommon malignancy, which makes accumulation of cases for a cohort difficult. The large volume of ES cases at MSKCC thus has allowed one of the largest cohorts published. In addition, all patients in this the present study had newly diagnosed ES, not restaging studies. This allowed evaluation of bone scan and PET/CT in the initial staging of ES. The weaknesses of the present study include the retrospective study design and possible selection bias. Retrospective studies introduce inherent biases that are difficult to overcome, including nonstandardized criteria for interpretation of the original studies. There may have been selection bias in the cohort, because not all patients with newly diagnosed ES underwent both PET/CT and bone scan during the defined time period. The present study addresses initial staging of ES, not the role of FDG PET/CT or bone scan on monitoring response to therapy. In summary, prior studies have suggested that FDG PET/CT is superior to MDP bone scan for detection of ES metastases. The present study has shown that this may not be true for ES when the primary malignancy is sclerotic on CT, a less common but encountered ES morphology. This retrospective trial suggests that bone scan may be omitted from the staging of newly diagnosed ES when the primary tumor is lytic on FDG PET/CT. When the primary ES is sclerotic, MDP bone scan may detect osseous metastases that are missed on FDG PET/CT. References 1. Potratz J, Dirksen U, Jürgens H, Craft A. Ewing sarcoma: clinical state-of-the-art. Pediatr Hematol Oncol 2012; 29:1–11 2. Grier HE. The Ewing family of tumors: Ewing’s sarcoma and primitive neuroectodermal tumors. Pediatr Clin North Am 1997; 44:991–1004
3. Paulussen M, Ahrens S, Burdach S, et al.; European Intergroup Cooperative Ewing Sarcoma Studies (EICESS). Primary metastatic (stage IV) Ewing tumor: survival analysis of 171 patients from the EICESS studies. Ann Oncol 1998; 9:275–281 4. Bernstein ML, Devidas M, Lafreniere D, et al. Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children’s Cancer Group Phase II Study 9457—a report from the Children’s Oncology Group. J Clin Oncol 2006; 24:152–159 5. Völker T, Denecke T, Steffen I, et al. Positron emission tomography for staging of pediatric sarcoma patients: results of a prospective multicenter trial. J Clin Oncol 2007; 25:5435–5441 6. Reinus WR, Gehan EA, Gilula LA, Nesbit M. Plain radiographic predictors of survival in treated Ewing’s sarcoma. IESS Committee. Skeletal Radiol 1992; 21:287–291 7. National Comprehensive Cancer Network. Ewing’s sarcoma family of tumors. In: NCCN clinical practice guidelines in oncology (NCCN Guidelines®): bone cancer, version 1.2014. www. nccn.org/professionals/physician_gls/pdf/bone. pdf. Published September 24, 2013. Accessed December 12, 2013 8. Meyer JS, Nadel HR, Marina N, et al. Imaging guidelines for children with Ewing sarcoma and osteosarcoma: a report from the Children’s Oncology Group Bone Tumor Committee. Pediatr Blood Cancer 2008; 51:163–170 9. Györke T, Zajic T, Lange A, et al. Impact of FDG PET for staging of Ewing sarcomas and primitive neuroectodermal tumours. Nucl Med Commun 2006; 27:17–24 10. Furth C, Amthauer H, Denecke T, Ruf J, Henze G, Gutberlet M. Impact of whole-body MRI and FDG-PET on staging and assessment of therapy response in a patient with Ewing sarcoma. Pediatr Blood Cancer 2006; 47:607–611 11. Daldrup-Link HE, Franzius C, Link TM, et al. Whole-body MR imaging for detection of bone metastases in children and young adults: comparison with skeletal scintigraphy and FDG PET. AJR 2001; 177:229–236
12. Franzius C, Sciuk J, Daldrup-Link HE, Jürgens H, Schober O. FDG-PET for detection of osseous metastases from malignant primary bone tumours: comparison with bone scintigraphy. Eur J Nucl Med 2000; 27:1305–1311 13. Walter F, Czernin J, Hall T, et al. Is there a need for dedicated bone imaging in addition to 18F-FDG PET/CT imaging in pediatric sarcoma patients? J Pediatr Hematol Oncol 2012; 34:131–136 14. Treglia G, Salsano M, Stefanelli A, Mattoli MV, Giordano A, Bonomo L. Diagnostic accuracy of 18F-FDG-PET and PET/CT in patients with Ewing sarcoma family tumours: a systematic review and a meta-analysis. Skeletal Radiol 2012; 41:249–256 15. Newman EN, Jones RL, Hawkins DS. An evaluation of [F-18]-fluorodeoxy-d-glucose positron emission tomography, bone scan, and bone marrow aspiration/biopsy as staging investigations in Ewing sarcoma. Pediatr Blood Cancer 2013; 60:1113–1117 16. Gerth HU, Juergens KU, Dirksen U, Gerss J, Schober O, Franzius C. Significant benefit of multimodal imaging: PET/CT compared with PET alone in staging and follow-up of patients with Ewing tumors. J Nucl Med 2007; 48:1932–1939 17. Tateishi U, Yamaguchi U, Seki K, Terauchi T, Arai Y, Kim EE. Bone and soft-tissue sarcoma: preoperative staging with fluorine 18 fluorodeoxyglucose PET/CT and conventional imaging. Radiology 2007; 245:839–847 18. Franzius C, Daldrup-Link HE, Sciuk J, et al. FDG-PET for detection of pulmonary metastases from malignant primary bone tumors: comparison with spiral CT. Ann Oncol 2001; 12:479–486 19. Charest M, Hickeson M, Lisbona R, Novales-Diaz JA, Derbekyan V, Turcotte RE. FDG PET/CT imaging in primary osseous and soft tissue sarcomas: a retrospective review of 212 cases. Eur J Nucl Med Mol Imaging 2009; 36:1944–1951 20. Cook GJ, Houston S, Rubens R, Maisey MN, Fogelman I. Detection of bone metastases in breast cancer by 18FDG PET: differing metabolic activity in osteoblastic and osteolytic lesions. J Clin Oncol 1998; 16:3375–3379 21. Kaste SC. Imaging pediatric bone sarcomas. Radiol Clin North Am 2011; 49:749–765, vi–vii
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FDG PET/CT and MDP Bone Scan in Ewing Sarcoma
A
B
C Fig. 1—32-year-old man with Ewing sarcoma (ES) with bone metastases detected on 18F-FDG PET/CT but not on methylene diphosphonate (MDP) bone scan. A, Posterior and anterior planar bone scan images show abnormal MDP uptake in left scapula representing primary ES (arrows). B, FDG PET/CT maximum intensity projection image shows not only abnormal uptake in left scapula primary ES (arrow) but also multiple osseous metastases (arrowheads) in spine and upper and lower extremities. Primary malignancy was lytic on CT (not shown). C, Axial CT (left) and fused PET/CT (right) images of left humerus show FDG-avid osseous metastasis (arrowhead) slightly misregistered from CT. En bloc resection of left humeral lesion yielded diagnosis of metastatic ES on pathology.
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Ulaner et al.
B
A
C
D
E
Fig. 2—35-year-old woman with Ewing sarcoma (ES). Bone metastases detected on methylene diphosphonate (MDP) bone scan but not on 18F-FDG PET/CT. A, FDG PET/CT maximum intensity projection image shows left clavicular primary ES (arrow). B, Axial CT (left) and fused PET/CT (right) images of left clavicular primary ES show that associated left shoulder soft-tissue mass (arrows) is FDG avid, whereas sclerotic osseous lesion (arrowheads) is not. C, Axial CT (left) and fused PET/CT (right) images of L1 vertebral body show non–FDG-avid mild sclerosis (arrows), considered nonspecific on PET/CT. D, Posterior and anterior planar MDP bone scan images show not only left clavicular primary ES (arrows) but also multiple osseous metastases (arrowheads) in L1 vertebral body, posterior right rib, and right ilium. E, Repeat bone scan after chemotherapy shows resolution of MDP-avid metastases. MDP is seen in right chest wall MediPort catheter (curved arrow).
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FDG PET/CT and MDP Bone Scan in Ewing Sarcoma
F
G Fig. 2 (continued)—35-year-old woman with Ewing sarcoma (ES). Bone metastases detected on methylene diphosphonate (MDP) bone scan but not on 18F-FDG PET/CT. F, Postchemotherapy axial CT (left) and fused PET/CT (right) images show resolution of FDG-avid left shoulder mass (arrows). Non–FDG-avid sclerotic clavicular lesion remains (arrowheads). Physiologic FDG avidity is seen in vocal cords (curved arrow). G, Postchemotherapy axial CT (left) and fused PET/CT (right) images show increased sclerosis of L1 vertebral body (arrow) consistent with healing of osseous metastases. FDG-avid bone marrow repopulation in left aspect of vertebra (arrowhead) is absent in healing metastasis.
Fig. 3—14-year-old girl with primary Ewing sarcoma with pelvic lymph node metastasis detected on 18F-FDG PET/CT. Axial CT (left) and fused PET/CT (right) images of right thigh soft tissues. An FDG-avid lymph node (arrows) in right pelvis is less than 1 cm in short axis and easily overlooked without addition of FDG PET. Lymph node metastasis was subsequently confirmed on biopsy.
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B
C Fig. 4—Venous thrombus detected on 18F-FDG PET/CT in same patient as in Fig. 3. A, Coronal CT (left) and fused PET/CT (right) images show linear FDG-avid expansion and filling of right femoral vein (arrows) representing venous thrombus. Primary right thigh soft-tissue Ewing sarcoma (arrowheads) is also shown. B, Coronal CT (left) and fused PET/CT (right) images at level of heart show FDG-avid low-attenuation thrombus (arrows) in right ventricle. C, Right ventricle thrombus (arrow) was confirmed on cardiac MRI (inversion recovery T1 with fat saturation).
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FDG PET/CT and MDP Bone Scan in Ewing Sarcoma
Newly diagnosed ES Staging with FDG PET/CT
Primary ES on FDG PET/CT is osseous and lytic No MDP bone scan is performed
Primary ES on FDG PET/CT is osseous and sclerotic
Primary ES on FDG PET/CT is soft tissue (not osseous)
MDP bone scan is added for osseous staging
Fig. 5—Proposed algorithm for staging of newly diagnosed Ewing sarcoma (ES) with 18 F-FDG PET/CT and methylene diphosphonate (MDP) bone scan.
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