Zhu YL, Sun YW, Ge YC, He J, Li RT. Advances in 18F-fluorodeoxyglucose positron emission tomography/computed tomography for soft tissue sarcomas. World J Radiol 2025; 17(7): 106427 [DOI: 10.4329/wjr.v17.i7.106427]
Corresponding Author of This Article
Jian He, MD, PhD, Associate Professor, Chief Physician, Department of Nuclear Medicine, Nanjing Drum Tower Hospital, Drum Tower Clinical Medical College, Nanjing Medical University, No. 321 Zhongshan Road, Nanjing 210008, Jiangsu Province, China. hjxueren@126.com
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Nuclear Science & Technology
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Yan-Lin Zhu, Yi-Wen Sun, Jian He, Department of Nuclear Medicine, Nanjing Drum Tower Hospital, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing 210008, Jiangsu Province, China
Yu-Chen Ge, Ru-Tian Li, The Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, Jiangsu Province, China
Author contributions: He J and Zhu YL conceived the idea for the manuscript; Zhu YL reviewed the literature and drafted the manuscript; Sun YW and Ge YC provided comprehensive perspectives; He J and Li RT revised and finalized the manuscript, and contributed equally as co-corresponding authors; and all authors have read and approved the final version of the manuscript. Justification for Co-Corresponding Authorship: He J and Li RT qualify as co-corresponding authors due to their indispensable, complementary, and equally critical leadership roles throughout the development and completion of this manuscript. He J was instrumental in originating the core concept of the manuscript and provided overarching intellectual guidance and supervision across all stages of the project. He spearheaded the critical revision process, ensuring the manuscript's scientific rigor, structural coherence, and alignment with the original research vision, ultimately playing the lead role in finalizing the content for submission. Li RT made pivotal contributions to the intellectual framing and scholarly depth of the work. She led the comprehensive revision efforts, focusing on enhancing theoretical synthesis, contextualizing findings within the broader literature, and refining the manuscript's narrative flow and academic impact. Her expertise was crucial in shaping the final version to meet high publication standards. The synergistic collaboration between He J and Li RT – combining He J's foundational conceptualization and strategic oversight with Li RT's profound analytical refinement and scholarly articulation – was fundamental to the successful preparation and completion of this manuscript. Both authors share equal responsibility for correspondence and the overall integrity of the work.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jian He, MD, PhD, Associate Professor, Chief Physician, Department of Nuclear Medicine, Nanjing Drum Tower Hospital, Drum Tower Clinical Medical College, Nanjing Medical University, No. 321 Zhongshan Road, Nanjing 210008, Jiangsu Province, China. hjxueren@126.com
Received: February 26, 2025 Revised: April 26, 2025 Accepted: July 16, 2025 Published online: July 28, 2025 Processing time: 149 Days and 20.3 Hours
Abstract
Soft tissue sarcomas (STS) are rare malignant tumors originating from mesodermal tissues with a poor prognosis, accounting for approximately 1% of all malignancies and comprising around 50 distinct subtypes. Conventional imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), primarily provide anatomical information, whereas 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) integrates functional metabolic and anatomical imaging, serving as a critical complementary tool in the diagnosis and management of STS. This article reviews recent advances in the application of 18F-FDG PET/CT for STS. The advantages of 18F-FDG PET/CT in STS include: (1) Early detection of metabolic activity changes in tumors, particularly when morphological alterations are insignificant; (2) Effective differentiation between benign and malignant soft tissue tumors, as well as aiding in distinguishing high-grade from low-grade sarcomas; (3) Identification of occult metastatic lesions, improving staging accuracy, and facilitating restaging in cases of recurrence or metastasis; (4) Utilization of parameters such as maximum standardized uptake value and metabolic tumor volume to assist in tumor grading and prognostic evaluation; and (5) Monitoring treatment response to guide adjustments in personalized therapeutic strategies. However, 18F-FDG PET/CT has limitations in diagnosis of certain STS subtypes (e.g., myxoid liposarcoma), detection and biopsy of metastatic lymph nodes, necessitating integration with clinical evaluation and other imaging techniques. 18F-FDG PET/CT is poised to play an increasingly vital role in the precision diagnosis and treatment of STS.
Core Tip:18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), which integrates both anatomical and metabolic imaging, provides comprehensive, accurate, and valuable information for clinical practice in soft tissue sarcomas (STS) safely and non-invasively. It has demonstrated significant advantages in various aspects of STS management, including diagnosis, tumor grading and staging, guidance for biopsy site selection, evaluation of treatment response, monitoring of recurrence and metastasis, and prognostic assessment. Therefore, 18F-FDG PET/CT can serve as a complementary tool to conventional imaging modalities such as computed tomography, magnetic resonance imaging, and bone scans.
Citation: Zhu YL, Sun YW, Ge YC, He J, Li RT. Advances in 18F-fluorodeoxyglucose positron emission tomography/computed tomography for soft tissue sarcomas. World J Radiol 2025; 17(7): 106427
Soft tissue sarcomas (STS) are rare and diverse malignant tumours of mesodermal origin, with a poor prognosis. They represent only approximately 1% of all malignant tumours and consist of over 50 different subtypes. In adults, the most common histological subtype is liposarcoma, followed by leiomyosarcoma and undifferentiated pleomorphic sarcoma[1]. In children, the most common histological subtype is rhabdomyosarcoma[2]. Clinically, STS presents as a heterogeneous soft tissue mass that grows over time, most often in the limbs or trunk. These lesions are often initially detected by ultrasound, and when STS is suspected, further investigation using magnetic resonance imaging (MRI) is recommended to characterise the lesion[3]. Conventional imaging modalities such as computed tomography (CT) and MRI can assess the anatomical structure of the malignant tumour, whereas 18F-fludeoxyglucose (18F-FDG) Positron emission tomography (PET)/CT, which integrates PET functional metabolic images with CT anatomical images, offers additional advantages. It can detect malignant tumours earlier than conventional imaging, often before significant morphological changes are evident in the lesions[4], identify occult lesions that may be overlooked or poorly visualised by conventional imaging, assess the extent of disease involvement throughout the body by only one scan, and provide valuable complementary information to conventional imaging. 18F-FDG PET/CT has demonstrated significant value in the diagnosis and differentiation, grading and staging, biopsy localization, treatment efficacy evaluation, recurrence and metastasis monitoring, and prognosis assessment of STS. This article will provide a comprehensive overview of the current applications and advances of 18F-FDG PET/CT in the field of STS.
18F-FDG PET/CT FOR THE DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS OF STS
Diagnosis of malignancy by conventional imaging methods often demands extensive experience and may still result in the oversight of critical malignant lesions[5]. In contrast, 18F-FDG PET/CT leverages the higher glycolytic activity of tumour cells compared to normal cells, typically manifesting as abnormally high 18F-FDG uptake at the lesion site. This metabolic feature enables 18F-FDG PET/CT to assist in the identification and diagnosis of soft STS lesions[6]. A retrospective study by Muheremu et al[7] involving 255 patients with STS demonstrated that 18F-FDG PET/CT, based on the maximum standardised uptake value (SUV), achieved diagnostic sensitivities of 96.6% for primary STS, 94.3% for recurrent STS, and 86.5% for metastatic STS. The results of a meta-analysis study by Younis et al[8] that included 21 studies showed that the combined use of 18F-FDG PET and CT for sarcoma detection achieved sensitivities and specificities of 89.2% and 76.3%, respectively. 18F-FDG PET improves the accuracy of STS diagnosis when combined with CT. Charest et al[9] retrospectively evaluated 212 patients with STS or osteosarcoma who underwent 18F-FDG PET/CT for initial staging or recurrence assessment, and revealed that 18F-FDG PET/CT detected 93.9% of STS or osteosarcomas with a sensitivity of 93.7% for STS. Thus, 18F-FDG PET/CT imaging, by integrating metabolic and morphological information, offers high sensitivity and specificity for detecting various STS.
In terms of differential diagnosis, 18F-FDG PET/CT is useful in distinguishing STS from other benign soft tissue lesions, such as inflammatory lesions or benign tumors, which typically do not exhibit significant metabolic activity. Nose et al[10] evaluated 54 soft tissue lesions in 47 patients and found a statistically significant difference in SUVmax between malignant and benign lesions (P < 0.001), suggesting that 18F-FDG PET/CT can effectively differentiate between malignant and benign soft tissue lesions. Suzuki et al[5]. retrospectively analyzed the imaging of 32 patients with lipomas (including one fibrolipoma and one angiolipoma) and 25 patients with liposarcomas (including 10 well-differentiated, 10 myxoid, and five other types). Their results demonstrated that in 18F-FDG PET analyzes, the mean SUV of malignant tumours was significantly higher than that of benign lesions (P < 0.0001). Receiver operating characteristic (ROC) curve analysis revealed an optimal cutoff value of 0.81 for distinguishing liposarcomas from benign lesions. Amini et al[11] retrospectively evaluated the diagnostic performance of 18F-FDG PET/CT in distinguishing STS from benign fluid collections (BFs), and reported significantly higher SUVmax values for STS (median 10.7, range 2.0-33.7) compared to BFs (median 2.8, range 1.1-12.3), concluded that 18F-FDG PET/CT was a sensitive modality for differentiating between STS and BFs, and that classification schemes based on SUVmax alone or SUVmax combined with FDG spatial distribution patterns can be used to distinguish STS from BFs. Collectively, these studies highlighted the utility of 18F-FDG PET/CT in differentiating STS from benign lesions.
While abnormally high FDG uptake is generally indicative of malignant tumours with a propensity for recurrence or progression, 18F-FDG PET/CT has limitations that may result in false-positive or false-negative findings, warranting further investigation. For example, aggressive benign tumours and inflammatory lesions can also show high FDG uptake on 18F-FDG PET/CT, leading to false positive results[12]. Common false-positive lesions include pigmented choroidal nodular synovitis, nodular disease, fibroma, neurofibroma, nerve sheath tumour, ligamentous fibromatosis, giant cell tumour, osteoid osteoma, Langerhans cell histiocytosis, chondroblastoma, endogenous chondrosarcoma, non-osteosinomatous fibroblastoma, and infection. Conversely, certain low-grade sarcomas with low metabolic activity may be underdetected on PET images due to their less pronounced glycolytic phenotype, such as well-differentiated and myxoid liposarcomas. In addition, Lunn et al[13] reported that intramuscular myxoma and myxoid liposarcoma often display low FDG activity on 18F-FDG PET/CT. Schwarzbach et al[14] found that recurrent well-differentiated liposarcomas may result in false-negative diagnoses on FDG PET. Therefore, 18F-FDG PET/CT is not recommended for staging, response assessment or surveillance in these histotypes, and MRI should be considered for diagnosis[1].
In STS, although metabolic information alone may be insufficient to accurately differentiate between benign lesions and malignant tumours, additional clinical and imaging features, such as patient age, tumour location, and morphological characteristics, can help narrow the differential diagnosis.
MULTIPARAMETRIC 18F-FDG PET/CT IN STS PATHOLOGICAL ASSESSMENT AND STAGING
18F-FDG PET/CT for grading and classification of STS
Pathological grading of STS is crucial for the diagnosis and treatment, which directly affects the choice of treatment strategies and prognostic assessment, and is the most important predictor of STS-related metastasis and mortality. 18F-FDG PET/CT can not only assist in distinguishing benign from malignant lesions, but also serve as an adjuvant for the pathological grading of STS. Although histological examination is the gold standard for grading STS, it has certain limitations, such as sampling bias and subjectivity. In recent years, 18F-FDG PET/CT has shown great potential in assisting the pathological grading of sarcomas. Previous studies have confirmed a significant correlation between the histological grading of STS and metabolic parameters[15]. The relationship between 18F-FDG uptake and pathological grading of STS was reported for the first time in 1988[16]. A study by Fendler et al[17] found that SUVmax, SUVpeak, SUVmax/SUVliver, and SUVpeak/SUVliver were well correlated with the grading of STSs at the time of initial diagnosis, and among these features, SUVpeak/SUVliver had the optimal efficacy in distinguishing low-grade from high-grade lesions, with ROC curve analysis showing an optimal threshold of 2.4, sensitivity of 79%, specificity of 81%, and an area under the curve (AUC) of 0.82. A study carried out by Benz et al[18] found that the STS glycolytic phenotype was significantly correlated with histological grading, and that SUVmax was statistically significantly different in tumours of different grades, regardless whether a 3-tier or 2-tier grading system was used (P < 0.001 for both). Jo et al[19] investigated preoperative 18F-FDG PET/CT imaging between January 2001 and February 2020 in patients undergoing initial surgery for retroperitoneal sarcoma at Samsung Medical Center, and the findings revealed that SUVmax correlated with tumour grade (P < 0.001, Spearman's coefficient: 0.627). A large retrospective audit of 18F-FDG PET/CT of different grades of bone and STSs carried out by Macpherson et al[20] at a single cross-regional centre found that high-grade (grade 2/3) bone and STSs were associated with a high SUVmax, particularly undifferentiated pleomorphic sarcomas, leiomyosarcoma, translocation-related sarcomas (Ewing’s sarcoma, synovial sarcoma, alveolar rhabdomyosarcoma), dedifferentiated liposarcomas, and osteosarcomas. Lower SUVmax values were observed in low histological grade (grade 1) sarcomas and rare subtypes of intermediate-grade soft-tissue sarcomas (e.g., alveolar soft part sarcoma and solitary fibrous tumor). Similarly, a retrospective study of STS patients by Reyes Marlés et al[15] found that SUVmax helped to differentiate between high-grade and low-grade STS. Charest et al[9] retrospectively evaluated 212 consecutive patients with known STS or bone sarcomas who underwent 18F-FDG PET/CT studies, the ROC analysis revealed an AUC of 94% for 18F-FDG PET/CT in distinguishing low-grade from high-grade sarcomas, suggesting that 18F-FDG PET/CT imaging, combining metabolic and morphological information, can accurately differentiate newly diagnosed low-grade and high-grade sarcomas. A study conducted by Tateishi et al[21] confirmed that increased glucose metabolism (determined by SUV) served as a strong indicator of tumor grading in bone and STS. Although high-grade tumors generally exhibit higher SUV values compared to low-grade tumors, low SUV values can still be observed in some grade 2-3 tumors, meaning that a low SUV cannot rule out the possibility of high-grade sarcomas[1].
Tumor metabolic parameters may also help differentiate histological subtypes. A study by Benz et al[18], which included 102 patients with 12 STS subtypes, found significant differences in SUVmax among histological subtypes (P = 0.03). High glycolytic phenotypes were observed in certain STS subtypes, such as malignant peripheral nerve sheath tumors, desmoid tumors, and dedifferentiated liposarcomas. In contrast, low glycolytic phenotypes (SUVmax < 2.5 g/mL) were observed in some other STS subtypes, including myxoid liposarcoma and gastrointestinal stromal tumors.
Additionally, literature has reported correlations between tumor metabolic parameters on PET scans and other pathological markers. Rakheja et al[22] retrospectively evaluated 238 consecutive patients with known STS or bone sarcomas who underwent 18F-FDG PET/CT for initial staging or recurrence assessment. Their study concluded that statistically significant correlations exist between mitotic count and SUVmax, as well as between the presence of tumor necrosis and SUVmax. Associating SUVmax with histological biomarkers that play important roles in STS grading systems may improve grading accuracy.
18F-FDG PET/CT improves STS staging and restaging
18F-FDG PET/CT is a valuable tool for assessing distant metastases in malignant tumors[23]. In patients with high-grade or aggressive tumours, systemic evaluation by 18F-FDG PET/CT is valuable to help determine the presence of distant metastases, especially skip lesions or occult metastases[24]. 18F-FDG PET/CT has been proven effective in the staging process of various malignancies. Similarly, its application in detecting regional and distant metastases in STS contributes to accurate staging. A prospective study by Metser et al[25] involving 304 patients with bone and STSs demonstrated that 18F-FDG PET/CT detected more metastatic lesions compared to conventional imaging (X-ray, CT, MRI, ultrasound) in patients considered for curative or salvage therapy, altering the initial staging in one-third of cases. A study by Elmanzalawy et al[26], which included 26 pediatric STS patients (median age 6 years), found that 18F-FDG PET/CT identified more lymph node metastases, particularly in non-enlarged lymph nodes, compared to concurrent CT and MRI. The study also recommended 18F-FDG PET/CT for initial evaluation in pediatric STS.
Not only in the initial staging of STS, but 18F-FDG PET/CT also plays a significant role in detecting local recurrence and restaging. A retrospective study by Annovazzi et al[27] showed that 18F-FDG PET/CT correctly identified 79 out of 88 Locally recurrent STS cases. Although MRI detected more local recurrences than 18F-FDG PET/CT in head-to-head comparisons, MRI had a significantly higher false-positive rate. The study also noted that adjustments in staging and restaging based on 18F-FDG PET/CT impacted clinical management, particularly in in patients undergoing restaging, with the proportions of patients whose clinical management was altered being 16.4% and 29.9% in the staging and restaging groups, respectively.
Furthermore, 18F-FDG PET/CT has demonstrated value in the staging and restaging of specific STS subtypes, such as rhabdomyosarcoma, with higher accuracy than conventional imaging. A retrospective study by Klem et al[28] involving 24 rhabdomyosarcoma patients reported a sensitivity of 77% and specificity of 95% for 18F-FDG PET when using final clinical composite outcomes as the "gold standard". Similarly, Donner et al[29] highlighted the importance of 18F-FDG PET/CT in the staging and restaging of rhabdomyosarcoma through two pediatric cases. A retrospective study by Tateishi et al[30] on 35 rhabdomyosarcoma patients showed that 18F-FDG PET/CT had higher accuracy in TNM staging (86% vs 54%, P < 0.01) compared to conventional imaging (including bone scans, chest X-rays, whole-body CT, and MRI of the primary site), particularly in M staging (89% accuracy for 18F-FDG PET/CT vs 63% for conventional imaging).
Combining 18F-FDG PET/CT with conventional imaging can further improve the accuracy of clinical staging and restaging in STS, avoiding both overstaging and understaging, thereby facilitating the development of more rational treatment plans. A prospective study by Faizi et al[31] involving 20 resectable STS patients evaluated the role of 18F-FDG PET/CT and MRI in preoperative staging. The results showed that the accuracy of staging using a combination of PET/CT and MRI was 92.31%, which was higher than the accuracy of staging using MRI alone (84.62%), comfirming that the combination of PET/CT and MRI improves overall staging accuracy. Tateishi et al[32] retrospectively compared the accuracy of 18F-FDG PET/CT, 18F-FDG PET, conventional imaging, and the combination of 18F-FDG PET/CT with conventional imaging for tumor staging in bone and STSs. They found that the combination of 18F-FDG PET/CT and conventional imaging had significantly higher overall staging accuracy than 18F-FDG PET alone (P < 0.0001) and reduced overstaging in 3 patients (4%) compared to 18F-FDG PET/CT alone.
18F-FDG PET/CT GUIDES STS BIOPSY AND TREATMENT
18F-FDG PET/CT for targeting STS biopsy sites
Traditional biopsy methods, which rely on clinical experience and conventional imaging guidance, may fail to accurately reflect metabolically active tumor regions, thereby potentially compromising diagnostic accuracy. In contrast, the 18F-FDG PET/CT technique detects tumor cell metabolic activity using the radioactively labeled glucose analog 18F-FDG. Since malignant tumor cells typically exhibit high FDG uptake, these areas show intense radiotracer uptake on PET scans. When combined with the precise anatomical information provided by CT, 18F-FDG PET/CT enables the identification of optimal target areas for biopsy[3], accurately localizing the most metabolically active tumor regions. This approach overcomes the limitations of traditional biopsy methods, particularly in highly heterogeneous lesions[2], improving biopsy success rates and ensuring the acquisition of the most representative tissue samples for reliable pathological diagnosis. Previous studies have confirmed that 18F-FDG PET/CT-guided biopsies achieve higher success rates than CT-guided biopsies[4].18F-FDG PET/CT-guided biopsy is a feasible and accurate method for diagnosing malignant lesions, and novel radiopharmaceuticals for biopsy guidance are under investigation[4,33,34]. Authoritative guidelines also acknowledge the utility of 18F-FDG PET/CT in biopsies for malignancies, including sarcomas[1].
However, some scholars argue that 18F-FDG PET/CT-guided biopsy for metastatic lymph nodes in STS has limitations. A prospective study by Wagner et al[35] involving 28 sarcoma patients found that the positive predictive value of 18F-FDG PET/CT for diagnosing lymph node metastases was only 29%, therefore, they do not recommend using PET/CT as the basis for lymph node biopsy in sarcoma patients.
Personalized STS treatment guided by 18F-FDG PET/CT
The development of personalized treatment plans is crucial for STS patients, as tumor characteristics, growth rates, and responses to therapy may vary significantly among individuals. 18F-FDG PET/CT provides detailed information on tumor metabolic activity, which is essential for assessing treatment response and monitoring therapeutic efficacy. Pre-treatment 18F-FDG PET/CT scans can elucidate the lesion characteristics and metastatic status in STS patients, thereby supporting the determination of initial treatment strategies. Conducting 18F-FDG PET/CT both before and after treatment allows for the monitoring of residual or recurrent tumors, and the evaluation of treatment outcomes (e.g., reduction in tumor volume, decrease in metabolic activity, or identification of treatment-resistant areas). This enables timely modifications to the treatment to optimize therapeutic efficacy.
During the initial treatment phase, 18F-FDG PET/CT often helps refine treatment strategies for STS patients by more accurately determining the extent of tumor involvement throughout the body. A retrospective study by Elmanzalawy et al[26] showed that 18F-FDG PET led to changes in treatment plans in 19% (5/26) of patients due to the detection of additional tumor lesions compared to CT and MRI. A multicenter prospective study by Metser et al[25] involving 304 bone and STS patients found that 18F-FDG PET/CT resulted in changes in treatment intent in 64 out of 171 cases (37.4%) and alterations in treatment type in 56 cases (32.8%), most commonly shifting from surgical or combined surgical approaches to systemic therapy. Notably, 18F-FDG PET/CT not only modifies treatment strategies by identifying more lesions than conventional imaging but may also by reclassifying false-positive or indeterminate findings from conventional imaging as non-tumorous. A retrospective study by Annovazzi et al[27] on 282 STS patients revealed that among those whose treatment strategies were adjusted based on PET, 58.8% were due to upstaging, while 41.2% were due to downstaging.
Additionally, 18F-FDG PET/CT can provide valuable information for the surgical management of STS patients, such as tumour margins, potential metastatic lesions, and possible lymph node involvement. This information is critical for surgical planning, helping surgeons determine the extent and approach of the procedure, minimize unnecessary surgical trauma, and improve surgical success rates and patient quality of life. For example, if 18F-FDG PET/CT shows that the tumor is closely adjacent to critical organs or vascular structures, surgeons may opt for a more conservative approach or administer preoperative radiotherapy or chemotherapy to reduce tumor volume, thereby lowering surgical complexity and risk. Liu et al[36] analyzed data from 89 retroperitoneal liposarcoma patients, measuring metabolic tumor volume (MTV), total lesion glycolysis (TLG), and SUVmax. They suggested that 18F-FDG PET/CT-based imaging could guide the extent of surgical resection, and the volumetric preoperative information provided by 18F-FDG PET/CT enables surgeons to make more precise and personalized decisions. Furthermore, the study found that MTV and TLG correlated with intraoperative blood loss, indicating that these metrics may offer predictive value regarding surgical difficulty. Tateishi et al[32] retrospectively compared 18F-FDG PET/CT, 18F-FDG PET, conventional imaging, and the combination of 18F-FDG PET/CT with conventional imaging in 117 newly diagnosed bone and STS patients. They found that the combined use of 18F-FDG PET/CT and conventional imaging reclassified tumors from unresectable to resectable in 2 patients (2%). A study by Yokouchi et al[37], which included 7 STS patients undergoing surgery, found that the preoperative SUVmax of the tumors averaged 11.7 (range: 3.8-22.1). The mean SUVmax values were 2.2 (range: 0.3-3.8) at 1 cm from the tumor boundary, 1.1 (0.85-1.47) at 2 cm, 0.83 (0.65-1.15) at 3 cm, 0.7 (0.42-0.95) at 4 cm, and 0.64 (0.45-0.82) at 5 cm. When the SUVmax threshold was set at 1.0, tumor cells were absent in regions with SUVmax < 1.0, suggesting that 18F-FDG PET/CT could define safe surgical margins for STS resection. The European Society for Medical Oncology guidelines state that for advanced/metastatic disease, abdominal CT scans and bone scans or 18F-FDG PET must be performed before considering pulmonary metastasectomy to confirm that the metastases are "isolated"[1]. 18F-FDG PET/CT is an essential tool for confirming surgical indications.
In some clinical contexts, 18F-FDG PET/CT can facilitate the planning of radiotherapy, ensuring that radiation doses are concentrated on metabolically active tumor regions while minimizing damage to surrounding normal tissues. A study by Najem et al[38] demonstrated that integrating 18F-FDG PET with CT/MR images reduced inter- and intra-observer variability in gross tumor volume delineation for STS, thereby enhancing the reproducibility of the process.
In summary, 18F-FDG PET/CT plays an increasingly important role in the development of personalized treatment plans for STS, contributing to enhanced treatment customization and therapeutic outcomes.
18F-FDG PET/CT ASSESSES STS THERAPY RESPONSE
18F-FDG is a glucose analog that is avidly taken up by metabolically active tumor cells, appearing as hypermetabolic foci on PET imaging. Upon successful therapeutic intervention, the metabolic activity of tumor cells is often attenuated, resulting in a corresponding reduction in 18F-FDG uptake within the lesion, which serves as a reliable biomarker for evaluating treatment efficacy. Quantitative or semi-quantitative analysis of tracer uptake intensity enhances the accuracy of evaluating tumor necrosis rates and treatment outcomes. 18F-FDG PET/CT offers unique advantages in monitoring treatment response for STS. The guidelines from the United Kingdom National Centre for Computer Animation suggest that 18F-FDG PET/CT may help determine systemic treatment response, with changes in 18F-FDG uptake after the initial cycle and completion of neoadjuvant therapy serving as imaging biomarkers for histopathological tumor response (≥ 90%-95% tumor necrosis)[1]. Donner et al[29] proposed that in pediatric oncology, 18F-FDG PET/CT could aid in assessing treatment response for rhabdomyosarcoma patients by providing early metabolic insights, identifying non-responders, thereby facilitating timely adjustments to treatment strategies. A study by Vlenterie et al[39] involving 20 STS patients who underwent 18F-FDG PET/CT scans at 2 and 8 weeks after pazopanib treatment found that 14 out of 20 patients discontinued pazopanib due to radiological progression (non-responders, n = 12) or toxicity (n = 2). The results demonstrated that 18F-FDG PET/CT identified a significant proportion of early pazopanib non-responders in this cohort. Additionally, 18F-FDG PET/CT can differentiate residual viable tumor tissue from post-treatment necrosis or fibrosis, improving assessment accuracy, particularly when morphological changes in the tumor are not evident. With advancing research and technology, the application of 18F-FDG PET/CT in sarcoma treatment response evaluation is expected to achieve broader clinical adoption and enhanced precision.
18F-FDG PET/CT IN THE SURVEILLANCE OF RECURRENCE AND METASTASIS OF STS
Despite being multimodally treated, recurrence and metastasis remain critical factors affecting the prognosis of STS patients. Therefore, early detection of recurrence and metastasis is essential for improving treatment outcomes and prognosis. As a functional imaging modality, 18F-FDG PET/CT demonstrates unique sensitivity and specificity in monitoring STS recurrence and metastasis.
The primary curative treatment for STS is surgical resection. However, 40%-60% of patients experience local or distant recurrence after surgery. Thus, early detection and treatment of local recurrence are essential in STS management[40]. The local recurrence rate for STS ranges from 6% to 25%, with higher recurrence risks observed in histological subtypes such as angiosarcoma, leiomyosarcoma, myxofibrosarcoma, and dedifferentiated pleomorphic sarcoma[1]. Park et al[41] retrospectively compared MRI and 18F-FDG PET/CT in 20 STS patients with local recurrence after resection. The results showed that the sensitivity of MRI and 18F-FDG PET/CT was 90.0% and 95.0%, respectively, while the specificity was 97.7% and 95.5%, respectively. The positive predictive values were 85.7% and 76.0%, and the negative predictive values were 98.5% and 99.2%, respectively. The study concluded that both MRI and 18F-FDG PET/CT have comparable efficacy in detecting local recurrence of STS.
In monitoring metastasis of STS, 18F-FDG PET/CT also demonstrates unique advantages. Metastatic spread in STS is primarily hematogenous, with lung metastases accounting for approximately 75%-80% of cases[42]. Hagi et al[43] retrospectively analyzed clinical records, chest CT scans, and 18F-FDG PET/CT scans of 102 STS patients. The study found that 18F-FDG PET/CT was less effective in distinguishing metastatic lung nodules from benign nodules, particularly small ones. Follow-up with CT scans remains the preferred method for diagnosing lung nodules smaller than 5 mm. Therefore, chest CT is still the first-choice method for detecting pulmonary metastatic disease[44]. However, 18F-FDG PET/CT can help differentiate false-positive lesions detected by chest CT[45,46]. It has been reported that approximately 10% of STS patients develop bone metastases[47]. For patients with confirmed STS, whole-body 18F-FDG PET/CT is superior to other imaging modalities in detecting bone metastases[16]. A study by Al-Ibraheem et al[48] found that 18F-FDG PET/CT had higher diagnostic accuracy than CT alone in detecting recurrent bone and STSs, particularly excelling in identifying bone metastases. Alveolar soft part sarcoma, angiosarcoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma, and dedifferentiated liposarcoma are histological subtypes with higher incidence of bone metastases. The European Society of Musculoskeletal Radiology guidelines highlight the utility of 18F-FDG PET/CT in detecting bone metastases in these specific subtypes[1]. It is important to note that, despite the high incidence of bone metastasis in myxoid liposarcoma (occurring in 17% of patients and representing 56% of metastatic events)[49], the application of 18F-FDG PET/CT is limited due to the typically low FDG uptake in this subtype[1], whole-body or spinal MRI remains the optimal imaging technique for detecting the bone metastases in myxoid liposarcoma[50]. Lymph node metastases in STS are rare, accounting for approximately 3% of metastatic cases[42]. Therefore, in certain histological subtypes, positive lymph nodes detected by 18F-FDG PET/CT are highly likely to be false positives. However, lymph node metastases are more common in high-grade rhabdomyosarcoma, clear cell sarcoma, epithelioid sarcoma, angiosarcoma, and synovial sarcoma. The National Comprehensive Cancer Network guidelines for STS suggest that 18F-FDG PET/CT may be useful in detecting lymph node metastases in rhabdomyosarcoma[1]. Burkhard-Meier et al[51] retrospectively analyzed 18F-FDG PET/CT scans of 56 STS patients with radiologically suspicious lymph node metastases that were subsequently confirmed histologically. They found that the SUVmax on 18F-FDG PET/CT was significantly associated with lymph node metastasis (P < 0.001), indicating that SUVmax is an important parameter for distinguishing benign from metastatic lymph nodes. In certain histological subtypes of STS with an increased incidence of bone or lymph node metastases, 18F-FDG PET/CT scans may be warranted. The American College of Radiology recommends 18F-FDG PET/CT as a primary diagnostic tool for the detection and monitoring of metastasis[52].
However, 18F-FDG PET/CT has certain limitations in monitoring recurrence and metastasis of STS. For example, some low-grade STS may exhibit low metabolic activity, leading to reduced sensitivity of 18F-FDG PET/CT and potential false-negative results. A study by Schwarzbach et al[14] found that 18F-FDG PET/CT had a sensitivity of 86% and specificity of 100% for detecting recurrence in STS patients. While it is preferentially applicable for recurrence detection in pleomorphic, mixed, and higher-grade liposarcomas, false-negative diagnoses may occur in well-differentiated liposarcomas. Wagner et al[35] demonstrated that the sensitivity and specificity of 18F-FDG PET/CT for lymph node metastasis detection were insufficient at 57% and 52%, respectively. Therefore, in clinical practice, a comprehensive evaluation that integrates patient history, findings from other imaging modalities, and pathological results is essential to enhance the accuracy of metastasis monitoring.
APPLICATION OF 18F-FDG PET/CT IN PROGNOSTIC ASSESSMENT OF STS
The evaluation of 18F-FDG uptake in tumor tissue can provide prognostic information. Various metabolic parameters from PET, such as MTV, TLG, and SUV, can be used to predict outcomes in STS patients, such as progression-free survival (PFS) and overall survival (OS). High SUV, high MTV, and high TLG are generally correlated with poor prognosis. A retrospective study by Reyes et al[15] involving 83 STS patients found that SUVmax, SUVpeak, MTV, and TLG were predictive factors for OS. Liu et al[36] analyzed data from 89 retroperitoneal liposarcoma patients, measuring MTV, TLG, and SUVmax, and explored their correlation with prognosis. The study revealed statistically significant associations between MTV, TLG, SUVmax, with both OS and disease-free survival (DFS). MTV > 457.65 was identified as an independent prognostic factor for OS in retroperitoneal liposarcoma (P = 0.025). In a retrospective study by Andersen et al[53] involving 55 STS patients, the optimal cutoff values for MTV and TLG in predicting OS were 25.0 and 265.6, respectively. MTV and TLG values above these thresholds were associated with shorter OS (P = 0.02 and P < 0.001, respectively). Multivariate Cox proportional hazards regression analysis showed that TLG was an independent prognostic factor for OS (P < 0.05, hazard ratio 3.37). Another retrospective study by Kalisvaart et al[54], which included 31 STS patients, found that SUVmax and SUVpeak were significant predictors of OS (P = 0.004 and P = 0.006, respectively). Multivariate analysis revealed that SUVmax and SUVpeak were independent prognostic factors for OS in STS patients (P = 0.005 and P = 0.004, with hazard ratios of 1.29 and 1.36, respectively). Metser et al[25] prospectively studied 304 patients with bone and STSs and demonstrated that quantitative metabolic tumor parameters from 18F-FDG PET/CT (SUVmax, MTV, and TLG) were statistically significant in predicting both PFS and OS. A retrospective study by Fuglø et al[55] involving 30 high-grade bone sarcoma patients and 59 STS patients found that the 5-year survival rate was 81% for patients with SUVmax ≤ 10, compared to 33% for those with SUVmax > 10. The results indicated that SUVmax of the primary lesion is a strong prognostic factor for survival. A meta-analysis including 6 studies (comprising 514 STS and bone sarcoma patients) showed that high FDG uptake was significantly associated with poor prognosis[56]. A study by Lisle et al[57] evaluated the clinical value of pretreatment SUVmax on 18F-FDG PET/CT in predicting survival outcomes for 44 synovial sarcoma patients. They found that pretreatment SUVmax was an independent predictor of both OS and PFS (P = 0.005 and P = 0.006, with hazard ratios of 6.52 and 2.54, respectively). Patients with SUVmax > 4.35 had reduced disease-free survival. A retrospective analysis by Jo et al[19] involving 129 retroperitoneal sarcoma patients showed that those with SUVmax above the threshold had worse prognoses in terms of OS, local recurrence, and distant metastasis (P < 0.001). In addition to baseline SUVmax, changes in SUVmax before and after treatment are also effective indicators for assessing STS prognosis. For example, a study by Kasper et al[58] evaluating chemotherapy response in 27 high-risk STS patients demonstrated a statistically significant difference in PFS between patients with decreased SUV (responders) and those with increased or unchanged SUV (non-responders) (P = 0.0187).
CONCLUSION
In summary, 18F-FDG PET/CT, which integrates both anatomical and metabolic imaging, provides comprehensive, accurate, and valuable information for clinical practice in STS safely and non-invasively. It has demonstrated significant advantages in various aspects of STS management, including diagnosis, tumor grading and staging, guidance for biopsy site selection, evaluation of treatment response, monitoring of recurrence and metastasis, and prognostic assessment, with increasingly robust evidence-based medical evidence supporting its value (Table 1). Therefore, 18F-FDG PET/CT can serve as a complementary tool to conventional imaging modalities such as CT, MRI, and bone scans.
Table 1 Landmark Studies Establishing 18F-fludeoxyglucose positron emission tomography computed tomography value in soft tissue sarcoma management.
Macpherson RE, Pratap S, Tyrrell H, Khonsari M, Wilson S, Gibbons M, Whitwell D, Giele H, Critchley P, Cogswell L, Trent S, Athanasou N, Bradley KM, Hassan AB. Retrospective audit of 957 consecutive (18)F-FDG PET-CT scans compared to CT and MRI in 493 patients with different histological subtypes of bone and soft tissue sarcoma.Clin Sarcoma Res. 2018;8:9.
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Burkhard-Meier A, Jurinovic V, Berclaz LM, Albertsmeier M, Dürr HR, Klein A, Knösel T, Di Gioia D, Unterrainer LM, Schmidt-Hegemann NS, Ricke J, von Bergwelt-Baildon M, Kunz WG, Lindner LH. Differentiation of benign and metastatic lymph nodes in soft tissue sarcoma.Clin Exp Metastasis. 2024;41:131-141.
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