Primary malignant bone tumors have an elevated rate of glycolysis and, consequently, a high uptake of 18F-FDG in malignant cells. Yet, FDG uptake alone is not adequate for characterization of primary bone tumors. Also, CT modality relies on morphological criteria as size and contrast enhancement pattern that does not accurately reflect the presence of active malignant conditions. The hybrid imaging modality PET/CT allows assessing molecular as well as morphologic information at the same time. So, PET/CT represents an efficient tool for whole-body staging and re-staging within one imaging modality [13, 14].
After random selection of the 40 patients in this study, they were categorized according to the indication of PET/CT study into pre-treatment group (7 patients) for primary staging of the tumor and post-treatment group (33 patients) either for detection of recurrent tumor in 14 patients or assessment of treatment response in 19 patients.
El-Galaly et al. [15] considered that the advantages of PET/CT in the diagnosis of different stages of bone tumors were accurate localization of the lesion, detection of the smaller lesion, and differentiating the benign, malignant and different stages of the tumor.
In the pre-treatment group in our study, PET/CT had an effective role in changing the total TNM staging in 2 patients (28.6%) with sarcomas; CT scan defined lymph nodes that were considered malignant while PET/CT revealed no corresponding FDG avidity; PET/CT provides a non-invasive method for well-characterization of the lesions that help in systemic therapeutic decision-making [16].
In a study performed by Tateishi et al. [17] on 50 patients with histologically proven bone sarcomas, nodal metastasis was correctly assessed in 48 patients (96%) with PET/CT, in contrast to 46 patients (92%) with CT. By adding information from conventional imaging to the PET/CT findings in another study by Tateishi et al. [18], they could achieve accurate staging in 60 of 69 patients (87%), upstaging in (12%) and downstaging in (1%) of sarcoma patients.
In this study, PET/CT studies were performed in 33 patients after treatment, either radiation, chemotherapy, combined chemo-radiotherapy or surgery, to exclude the presence of any viable tumor; recurrent/or residual lesions, locoregional lymphadenopathy and distant metastatic lesions and also to assess the treatment response. Twenty eight patients (84.8% of them) underwent previous surgical excision of the tumors as the first choice of treatment of malignant bone tumors is surgical whether it is followed by medical treatment or not [19].
FDG-PET-CT is highly useful for monitoring response to therapeutic interventions. It can identify response to therapy earlier than any other imaging modality improving patient management by allowing termination of ineffective and toxic therapies. It allowed better evaluation of anatomic regions that have been previously treated by surgery or radiation in which the differentiation between post-treatment scar and recurrent tumor may be a big challenge [20].
We reported higher sensitivity of PET/CT compared to CT in detection of local tumor recurrence/residue, it has higher ability to differentiate between post-surgical tissue changes and early local recurrences, and also it was not affected by metallic artifacts which degraded the CT quality of image.
This study demonstrated PET/CT sensitivity of 94.4% and specificity of 86.7% with accuracy of 90.9% compared to CT sensitivity of 88.2% and specificity of 81.2% with accuracy of 84.8%. These results were comparable to those of Liu et al. [19] in their meta-analytical study of twenty six studies in the effectiveness of PET/CT in recurrence and metastases formation observations of osteosarcoma that reported PET/CT sensitivity of 91%, specificity of 90%, and accuracy of 94%.
Our results matched also with those of Schulte et al. [21] who studied 44 patients with malignant bone tumors showing PET/CT sensitivity of 93%, specificity of 76.7%, and accuracy of 81.7% in detecting recurrent disease and re-staging patients with primary bone tumors.
One of the false positive results in the present study was in the form of post-operative changes that was misdiagnosed as recurrent tumor, but resolved on follow-up. Kumar et al. [22] realized that post-surgical inflammatory oedema, scarring and granulation tissue can cause increased FDG uptake making the interpretation of PET/CT studies very difficult. Also, even if PET/CT is obtained after 12 weeks following completion of chemo-radiation, false-positive findings may still occur and are caused by post- chemo-radiation, inflammation, oedema, hyperaemia, fibrosis and loss of tissue planes and the presence of post-treatment inflammatory tissue can cause increased FDG uptake which may be misdiagnosed as residual tumor [23].
In one case in our study, multiple bone deposits have been developed in the form of FDG avidity with no corresponding anatomical changes on localization CT. In their study on the efficiency of PET/CT in evaluation of skeletal deposits, Wafaie et al. [24] detected a considerably large number of missed (false negative) lesions on CT images due to absence of any detectable structural abnormalities with a high metabolic activity of such lesions on fused PET/CT images. This is attributed to the ability of PET to detect bone marrow based metastases early and in the absence of morphologic changes on CT images; thus improving CT sensitivity.
Also, a lesion based analysis was performed in detailed retrograde matter for a total of 386 detected osseous lesions in a study performed by Ali and Abd Elkhalek [25] that showed higher sensitivity of PET/CT study than CT study alone (100% and 93.9% respectively) in detection of osseous metastases due to the presence of active osseous deposits without structural abnormalities, that were falsely interpreted as negative by CT.
In patients with bone sarcoma, the lungs are at highest risk for distant metastases. Franzius et al. [26] stated that PET alone is not sufficient for detection of small lung metastases likely due to respiratory movements during the PET acquisition. Other causes are that FDG-negative lung metastases can be small in size and have decreased FDG avidity.
According to the detected metastatic pulmonary nodules in this study, multiple nodules especially smaller than 1 cm were beyond PET resolution and had no corresponding FDG uptake and thus the PET-only scans were inferior to diagnostic CT for detecting lung lesions. So, the PET/CT protocol should include a diagnostic lung CT in bone tumors patients [27].
London et al. [28] compared PET/CT with conventional imaging (CT, MRI, ultrasound, and bone scan) in a study that included 314 lesions on 86 scans, they reported that PET/CT had a higher sensitivity (98% vs 83%) and specificity (97% vs 78%) than did conventional imaging for detecting distant metastases, with the exception of pulmonary nodules; regarding pulmonary nodules, PET/CT was found to have a higher specificity (96% vs 87%) but lower sensitivity (80% vs 93%) than did conventional imaging.
In those who underwent medical treatment in the present study, PET was able to detect regression in FDG avidity and decreased SUV in one patient with left iliac Ewing sarcoma which showed no CT morphological changes. Rashad et al. [29] in their study which performed FDG PET in 18 pediatric sarcoma patients prior to and after neoadjuvant chemotherapy that an overall tumor SUV and SUVmax. on post-treatment 18F-FDG PET/CT scans were more accurate for the assessment of treatment response than changes in tumor size.
This is considered one of the powerful advantages of FDG PET/CT; it can determine therapeutic response through early identification of bad responders [30]. This gives the chance to modify or extend preoperative chemotherapy while overcoming any delay related to surgery or histopathologic analysis of the resected specimen.
The main limitation in this study was the relative small number of included subjects that might cause some missed diagnosis and misdiagnosis not giving full idea about the diagnostic efficacy of PET/CT. Also, statistical tests could not be able to identify significant relationships within various data set, as the relationship between PET/CT findings and different types of primary malignant bone tumors.